JPH10147587A - 2-amino-1,3 propanediol derivative and its pharmaceutical use - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject new compound, comprising a specific 2-amino-1,3- propanediol derivative, having immunological activities and useful for treatment, prevention, etc., of rejection due to transplantation, a graft versus host reaction due to bone marrow transplantation, autoimmune diseases, psoriasis, etc. SOLUTION: This new 2-amino-1,3-propanediol derivative (salt) is represented by formula I [R<1> is H or an acyl; R<2> is H, a lower alkyl or an aryl; R<3> is H, a lower alkyl, a higher alkyl, etc.; R<4> is H, a (halo)lower alkyl, a higher alkyl, a (substituted)aryl, etc.; A is an alkylene; E is a bond, 0 or imino; G is a bond or an arylene; J is a bond or O; L is a bond or a lower alkylene] and is useful for treatment, prevention, etc., of a rejection due to transplantation, a graft versus host reaction due to bone marrow transplantation, autoimmune diseases, psoriasis, etc. The compound is obtained by carrying out the hydrosilylating reaction of an unsaturated compound represented by formula II (A<2> is same as A; Y<1> is a lower alkyl; X<5> is a halogen atom) with silanes represented by formula III and reducing the resultant compound represented by formula IV.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a novel 2-amino-
The present invention relates to a 1,3-propanediol derivative and a pharmaceutically acceptable salt thereof.

More specifically, the present invention relates to a novel 2-amino-1,3-propanediol derivative having immunosuppressive activity, a pharmaceutically acceptable salt thereof, a method for producing the same, a pharmaceutical composition containing the same, The present invention relates to a use as a medicine, and a method for treating and preventing transplant rejection, graft-versus-host disease due to bone marrow transplantation, autoimmune disease, psoriasis, and the like.

[0003]

An object of the present invention is to have an immunosuppressive activity,
Therefore, a novel 2-amino-1,3-propanediol derivative and a pharmaceutically acceptable salt thereof useful for treatment and prevention of transplant rejection, graft-versus-host disease due to bone marrow transplantation, autoimmune disease, psoriasis, etc. It is to provide.

It is another object of the present invention to provide 2-amino-1,3
-To provide a method for producing a propanediol derivative and a pharmaceutically acceptable salt thereof.

It is a further object of the present invention to provide a
An object of the present invention is to provide a pharmaceutical composition containing a 1,3-propanediol derivative and a pharmaceutically acceptable salt thereof as an active ingredient.

[0006] It is a further object of the present invention to provide the above-mentioned 2-amino-
Use of 1,3-propanediol derivatives and pharmaceutically acceptable salts thereof as pharmaceuticals, and treatment of transplantation rejection in humans or animals, graft-versus-host disease by bone marrow transplantation, autoimmune disease, psoriasis, etc. To provide a preventive method.

[0007] It is a further object of the present invention to provide the above-mentioned 2-amino-
By providing an agent for treating or preventing rejection by transplantation, graft-versus-host disease by bone marrow transplantation, autoimmune disease, psoriasis, etc., comprising a 1,3-propanediol derivative and a pharmaceutically acceptable salt thereof. is there.

[0008]

The 2-amino-1,3-propanediol derivative which is the object compound of the present invention is a novel compound having the following general formula (I):

[0009]

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[Wherein R ¹ represents a hydrogen atom or acyl, R ² represents a hydrogen atom, lower alkyl or aryl, R ³ represents a hydrogen atom, lower alkyl or higher alkyl, or R ² and R ³ Represents a linear or branched lower alkylene which is bonded, and R ⁴ represents a hydrogen atom, lower alkyl, mono (or di or tri) halo (lower) alkyl, higher alkyl, lower alkenyl, cyclo (lower)
Alkyl represents aryl optionally having one or more substituents, aryl (lower) alkyl optionally having one or more substituents, or a heterocyclic group; an alkylene or higher alkylene, E is bond, an oxygen atom or the formula -N (R ⁵⁾ - shows the imino group (wherein, R ⁵ represents a hydrogen atom or a lower alkyl) represented by, G is a bond or Arylene shows,
J represents a bond or an oxygen atom, and L represents a bond or a lower alkylene] [hereinafter, also referred to as target compound (I)].

The target compound (I) can include one or more stereoisomers due to an asymmetric carbon atom or a silicon atom, and all such isomers and their mixtures are also included in the scope of the present invention. It is.

Furthermore, the effects of light, acid, base and the like may cause isomerization or rearrangement of compound (I), and the compounds obtained as a result of such isomerization or rearrangement are also included in the scope of the present invention. It is.

[0013] Solvates (eg, hydrates) of compound (I) and any crystal forms of compound (I) are included in the scope of the present invention.

[0014]

BEST MODE FOR CARRYING OUT THE INVENTION The target compound (I) or a salt thereof can be produced by the method shown in the following reaction formula. Method 1

[0015]

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Method 2

[0017]

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(Wherein R ¹ , R ² , R ³ , R ⁴ , A,
E, G, J and L are as defined above, and Y ¹
Is a lower alkyl, R ¹ a is an acyl)

The starting compound (II) can be produced by the following method, the method described in the following Production Examples, or a method analogous thereto. Method A

[0020]

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[0021]

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Method B

[0023]

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Method C

[0025]

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[0026]

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(Wherein R ¹ , R ² , R ³ , R ⁴ , A,
E, G, J, L and Y ¹ are as defined above, R ⁵ a and R ⁵ b each represent a hydroxyl-protecting group, R ⁶ represents lower alkyl or lower alkylphenyl, X ¹ , X ² , X ³ , X ⁴ , X ⁵ , X ⁶ , X ⁷ and X ⁸ each represent a halogen atom, Y ² represents a leaving group, and A ¹ , A ² and A ³ each represent a lower alkylene or a higher alkylene. And A ⁴ represents lower alkylene)

The reaction of the above method can be carried out by the method described later in this specification or a method similar thereto.

Suitable pharmaceutically acceptable salts of the target compound (I) are conventional non-toxic salts and include salts with bases or acid addition salts, for example, alkali metal salts (eg, sodium salt, Salts with inorganic bases such as potassium salts), alkaline earth metal salts (eg, calcium salts, magnesium salts, etc.), ammonium salts; for example, organic amine salts (eg, triethylamine salts, pyridine salts, picoline salts, ethanolamine) Salts with organic bases such as salts, triethanolamine salts, dicyclohexylamine salts, N, N'-dibenzylethylenediamine salts; inorganic acid addition salts (eg, hydrochloride, hydrobromide, sulfate, phosphorus Acid carboxylate or sulfonic acid addition salt (eg, formate, acetate,
Trifluoroacetate, oxalate, maleate, tartrate, fumarate, methanesulfonate, benzenesulfonate, toluenesulfonate, etc.); basic or acidic amino acids (eg, arginine, aspartic acid, And glutamic acid).

In the foregoing and following description of the present specification, preferred examples of various definitions within the scope of the present invention will be described in detail below.

"Lower" refers to a group having 1 to 6 carbon atoms unless otherwise specified.
Is the meaning of The preferred "lower alkyl" moiety in "lower alkyl" and "lower alkylphenyl" is straight-chain or branched alkyl having 1 to 6 carbon atoms, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec. - butyl, tert- butyl, pentyl, hexyl and the like, preferably a C ₁ -C ₄ alkyl.

Suitable "mono (or di or tri) halo (lower) alkyl" are, for example, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, bromomethyl, dibromomethyl, tribromomethyl, 1- or 2-fluoroethyl, 1- or 2-bromoethyl, 1- or 2-
Chloroethyl, 1,1-difluoroethyl, 2,2-difluoroethyl, 3,3,3-trifluoropropyl and the like, preferably trifluoromethyl,
3,3-trifluoropropyl.

Preferred "lower alkylenes" have 1 to 6 carbon atoms.
Linear or branched alkylene, such as methylene, ethylene, trimethylene, propylene, tetramethylene, methylmethylene, methylethylene, methyltrimethylene, pentamethylene, hexamethylene and the like, preferably methylene, ethylene, Trimethylene or methylethylene.

"High grade" means that the carbon number is 7 to 2 unless otherwise specified.
It means 0. Preferred "higher alkyls" have 7 to 7 carbon atoms.
20 straight-chain or branched alkyl, such as heptyl, 2-methylheptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, 11-methyldodecyl, 12-methyltridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl, octadecyl, nonadecyl, etc. icosyl and the like, preferably C ₇ -C ₁₆ alkyl.

Preferred "higher alkylenes" are those having 7 to 2 carbon atoms.
0 linear or branched alkylene, such as heptamethylene, methylheptamethylene, octamethylene,
Nonamethylene, decamethylene, undecamethylene, dodecamethylene, tridecamethylene, tetradecamethylene,
Pentadecamethylene, hexadecamethylene methylene, heptadecamethylene, octadecamethylene, nonadecamethylene and Ikosamechiren the like, preferably C ₇ -C ₁₆ alkylene.

Preferred "lower alkenyl" has 2 to 6 carbon atoms.
Linear or branched alkenyl such as vinyl, 1-propenyl, allyl, isopropenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl pentenyl and the like, preferably C ₂ -C ₄ alkenyl.

Preferred "cyclo (lower) alkyl" is cycloalkyl having 3 to 6 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and the like.

Suitable "aryl" for R ² includes phenyl, naphthyl and the like, preferably phenyl.

Suitable "aryl (lower) alkyl" for R ⁴ is phenyl (lower) alkyl (eg, benzyl,
Phenethyl, phenylpropyl, etc.), naphthyl (lower) alkyl (eg, naphthylmethyl, naphthylethyl,
And the aryl (lower) alkyl group includes one or more (preferably 1 to 3) halogen atoms, amino, lower alkoxy, mono (or di or tri) halo (lower) ) It may have a substituent such as alkyl.

Suitable "aryl" for R ⁴ includes phenyl, naphthyl and the like, wherein the aryl group is one or more (preferably 1 to 3) halogen atoms, amino, lower alkyl, higher alkyl, It may have a substituent such as lower alkoxy, mono (or di or tri) halo (lower) alkyl.

The "halogen" moiety in the preferred "halogen atom" and "mono (or di- or tri) halo (lower) alkyl" includes chlorine, bromine, fluorine and iodine.

Preferred "lower alkoxy" is one having 1 to carbon atoms.
6 straight-chain or branched alkoxy, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, tert-butoxy, pentyloxy, tert-pentyloxy, hexyloxy and the like.

Preferred "lower alkanoyls" are those having 1 carbon atom
To 6 straight-chain or branched alkanoyls such as formyl, acetyl, propanoyl, butanoyl, 2-
Methylpropanoyl, 2,2-dimethylpropanoyl,
Hexanoyl and the like.

Suitable "arylene" includes phenylene, naphthylene and the like.

Preferred "heterocyclic groups" include saturated or unsaturated monocyclic or polycyclic heterocyclic groups containing at least one heteroatom such as an oxygen atom, a sulfur atom and a nitrogen atom. Particularly preferred heterocyclic groups include the following. Unsaturated 3- to 8-membered (preferably 5- or 6-membered) heteromonocyclic group containing 1-4 nitrogen atoms, such as pyrrolyl, pyrrolinyl, imidazolyl, pyrazolyl, pyridyl, dihydropyridyl, pyrimidinyl, pyrazinyl,
Pyridazinyl, triazolyl (eg, 4H-1,2,4-
Triazolyl, 1H-1,2,3-triazolyl, 2H
-1,2,3-triazolyl, etc.), tetrazolyl (eg, 1H-tetrazolyl, 2H-tetrazolyl, etc.)
A saturated 3-8 membered ring (preferably 5 or 6 membered) heteromonocyclic group containing 1-4 nitrogen atoms, such as pyrrolidinyl, imidazolidinyl, piperidyl, piperazinyl and the like; Containing unsaturated fused heterocyclic groups such as indolyl, isoindolyl, indolinyl, indolizinyl, benzimidazolyl, quinolyl,
Isoquinolyl, indazolyl, benzotriazolyl and the like; unsaturated 3- to 8-membered (preferably 5- or 6-membered) heteromonocyclic group containing 1-2 oxygen atoms and 1-3 nitrogen atoms, for example, Oxazolyl, isoxazolyl, oxadiazolyl (eg, 1,2,4-oxadiazazolyl,
1,3,4-oxadiazolyl, 1,2,5-oxadiazazolyl, etc.); a saturated 3- to 8-membered ring containing 1-2 oxygen atoms and 1-3 nitrogen atoms (preferably 5- or 6-membered) heteromonocyclic group such as morpholinyl, sydnonyl and the like; unsaturated fused heterocyclic group containing 1-2 oxygen atoms and 1-3 nitrogen atoms, such as benzooxazolyl, benzoxanol Diazolyl and the like; unsaturated 3- to 8-membered (preferably 5- or 6-membered) heteromonocyclic group containing 1-2 sulfur atoms and 1-3 nitrogen atoms, for example, thiazolyl, isothiazolyl, thiadiazolyl ( Example, 1, 2, 3
Thiadiazolyl, 1,2,4-thiadiazolyl, 1,
3,4-thiadiazolyl, 1,2,5-thiadiazolyl, etc.), dihydrothiazinyl and the like; a saturated 3- to 8-membered ring containing 1-2 sulfur atoms and 1-3 nitrogen atoms (preferably 5 or 6) Membered) heteromonocyclic groups such as thiazolidinyl; unsaturated 3 to 8 containing 1 to 2 sulfur atoms
Membered (preferably 5 or 6 membered) heteromonocyclic groups, such as thienyl, dihydrodithiynyl, dihydrodithionyl, etc .; unsaturated condensates containing 1-2 sulfur atoms and 1-3 nitrogen atoms Heterocyclic groups such as benzothiazolyl, benzothiadiazolyl and the like; unsaturated 3- to 8-membered (preferably 5- or 6-membered) heterocyclic monocyclic groups containing one oxygen atom, such as furyl; one oxygen Unsaturated 3- to 8-membered (preferably 5- or 6-membered) heteromonocyclic group containing one and two sulfur atoms, such as dihydrooxathiinyl; containing one to two sulfur atoms Unsaturated fused heterocyclic groups such as benzothienyl, benzodithiynyl and the like; 1
Unsaturated condensed heterocyclic groups containing one oxygen atom and one or two sulfur atoms, such as benzooxathiynyl.

Preferred "acyl" includes carbamoyl and aliphatic acyl groups. Preferred examples of the acyl include the following. Carbamoyl; and aliphatic acyls such as lower or higher alkanoyl (eg, formyl, acetyl, propanoyl, butanoyl, 2-methylpropanoyl, pentanoyl, 2,2-dimethylpropanoyl, hexanoyl, heptanoyl, octanoyl, nonanoyl, decanoyl, undecanoyl) , Dodecanoyl, tridecanoyl, tetradecanoyl, pentadecanoyl, hexadecanoyl, heptadecanoyl, octadecanoyl, nonadecanoyl, icosanoyl, etc.);
Lower or higher alkoxycarbonyl (eg, methoxycarbonyl, ethoxycarbonyl, tert-butoxycarbonyl, tert-pentyloxycarbonyl, heptyloxycarbonyl, etc.); lower or higher alkanesulfonyl (eg, methanesulfonyl, ethanesulfonyl, etc.); lower or higher Alkoxysulfonyl (eg, methoxysulfonyl, ethoxysulfonyl, etc.).

Preferred "leaving groups" include hydroxy, halogen atom (as exemplified above), sulfonyloxy (eg, methylsulfonyloxy, phenylsulfonyloxy, tolylsulfonyloxy, etc.), 2,4-dinitrophenoxy and the like. Is mentioned.

Suitable "hydroxyl protecting groups" include acyl groups such as tetrahydropyranyl and lower alkanoyl (eg, formyl, acetyl, propionyl, butyryl, isobutyryl, valeryl, isovaleryl, etc.).

Preferred embodiments of the target compound (I) include the following. R ¹ represents a hydrogen atom or a lower alkanoyl (more preferably C ₁ -C ₄ alkanoyl, particularly preferably acetyl); R ² represents a hydrogen atom or a lower alkyl (more preferably C ₁ -C ₄ alkyl); And particularly preferably methyl or ethyl) or aryl (more preferably phenyl)
Wherein R ³ is a hydrogen atom, lower alkyl (more preferably methyl, ethyl, propyl, butyl or hexyl) or higher alkyl (more preferably C ₇ -C _16).
Alkyl, particularly preferably octyl), or R ² and R ³ are bonded to form a linear or branched lower alkylene (more preferably C ₂ -C ₄ alkylene, particularly preferably tetraalkylene). R ⁴ is a hydrogen atom; lower alkyl (more preferably C 4
C ₁ -C ₄ alkyl, particularly preferably methyl, ethyl, propyl, isopropyl, butyl, isobutyl or tert-butyl); mono (or di or tri) halo (lower) alkyl (more preferably mono (or di) or tri) halo (C ₁ -C ₄ alkyl),
Higher alkyl (more preferably C ₇ -C ₁₆ alkyl, particularly preferably octyl); lower alkenyl (more preferably C ₂ -C ₄ alkenyl, particularly preferably trifluoromethyl). Is allyl); cyclo (lower) alkyl (more preferably cyclohexyl); even if it has 1 to 3 substituents selected from the group consisting of halogen atom, lower alkyl, higher alkyl and lower alkoxy A good aryl (more preferably a phenyl optionally having 1 to 3 substituents selected from the group consisting of a halogen atom, C ₁ -C ₆ alkyl, C ₇ -C ₁₆ alkyl and C ₁ -C ₄ alkoxy) And particularly preferably one selected from the group consisting of a chlorine atom, methyl, propyl, pentyl, heptyl and methoxy Have a substituent is phenyl); 1-3 lower alkoxy (more preferably C ₁ -C ₄ alkoxy, particularly preferably may have a methoxy) aryl ( lower) alkyl (more preferably C ₆ -C ₁₀ aryl (C ₁ -C
₄ alkyl), particularly preferably benzyl); or an unsaturated 3 to 3 alkyl group containing 1 to 2 sulfur atoms.
Represents an 8-membered (preferably 5- or 6-membered) heteromonocyclic group (more preferably thienyl), and A is a lower alkylene (more preferably trimethylene, propylene, tetramethylene, pentamethylene or hexamethylene) Or higher alkylene (more preferably C ₇ -C ₁₆₎
Alkylene, particularly preferably octamethylene, nonamethylene, decamethylene, undecamethylene, dodecamethylene or tridecamethylene) indicates, E is bond, an oxygen atom or the formula -N (R ⁵⁾ - imino represented by G represents a bond or an arylene (more preferably phenylene), wherein R ⁵ is a hydrogen atom or a lower alkyl (more preferably C ₁ -C ₄ alkyl, particularly preferably methyl). J) represents a bond or an oxygen atom, and L represents a bond or a lower alkylene (more preferably C ₁ -C ₄ alkylene, particularly preferably methylene, ethylene or trimethylene).

More preferred embodiments of the target compound (I) include the following. R ¹ represents a hydrogen atom, R ²
Represents lower alkyl (more preferably C ₁ -C ₄ alkyl, particularly preferably methyl or ethyl), and R ³ represents lower alkyl (more preferably C ₁ -C ₄ alkyl, particularly preferably methyl). Or R ⁴ is mono (or di or tri) halo (lower) alkyl (more preferably mono (or di or tri) halo (C ₁ -C ₄ alkyl), particularly preferably tri Or aryl (lower) alkyl (more preferably, 1 to 3 lower alkoxy (more preferably C ₁ -C ₄ alkoxy, particularly preferably methoxy)); C ₆
C ₁₀ aryl (C ₁ -C ₄ alkyl), particularly preferably benzyl), and A is lower alkylene (more preferably trimethylene, propylene, tetramethylene, pentamethylene or hexamethylene)
, E represents a bond, G represents an arylene (more preferably phenylene), J represents a bond, and L is a lower alkylene (more preferably C ₁ -C ₄ alkylene, particularly preferably Methylene, ethylene or trimethylene).

The method for producing the target compound (I) of the present invention is described in detail below. Method 1 The target compound (I) or a salt thereof can be produced by reducing the compound (II) or a salt thereof. Compound (I
Suitable salts of I) can be the same as those exemplified as the salts of compound (I). Examples of the reduction include reduction using alkali metal borohydride (eg, sodium borohydride, lithium borohydride, etc.), alkali metal aluminum hydride (eg, lithium aluminum hydride, etc.), and the like. This reaction usually involves alcohol (eg, methanol, ethanol,
The reaction is performed in a conventional solvent that does not adversely influence the reaction, such as propanol), tetrahydrofuran, dioxane, dimethyl sulfoxide, N, N-dimethylformamide or a mixture thereof. The reaction temperature is not particularly limited, and the reaction is usually performed under cooling to heating.

Method 2 Compound (Ib) or a salt thereof can be produced by subjecting compound (Ia) or a salt thereof to a deacylation reaction.
Suitable salts of compound (Ia) and compound (Ib) include the same as those exemplified as the salt of compound (I). Suitable methods for this reaction include:
Conventional methods such as hydrolysis and reduction may be mentioned.

(I) Hydrolysis The hydrolysis is preferably carried out in the presence of a base or an acid (including a Lewis acid). Suitable bases include alkali metals (eg, lithium, sodium, potassium, etc.) and their hydroxides (eg, lithium hydroxide or hydrate thereof).
Or carbonate or bicarbonate, trialkylamine (eg, trimethylamine, triethylamine, etc.),
Picoline, 1,5-diazabicyclo [4.3.0] non-5-ene, 1,4-diazabicyclo [2.2.2] octane, 1,8-diazabicyclo [5.4.0] undec-7- And inorganic bases such as ene and organic bases.

Suitable acids include organic acids (eg, formic acid, acetic acid, propionic acid, trichloroacetic acid, trifluoroacetic acid, etc.) and inorganic acids (eg, hydrochloric acid, hydrobromic acid, sulfuric acid, hydrogen chloride, hydrogen bromide) Etc.). The deacylation reaction using a Lewis acid such as trihaloacetic acid (eg, trichloroacetic acid, trifluoroacetic acid, etc.) is preferably performed in the presence of a cation scavenger (eg, anisole, phenol, etc.). The reaction is usually performed in a solvent such as water, alcohol (eg, methanol, ethanol, etc.), methylene chloride, tetrahydrofuran, a mixture thereof or any other solvent which does not adversely influence the reaction. Liquid bases or acids can also be used as solvents. The reaction temperature is not particularly limited, and the reaction is usually performed under cooling to heating.

(Ii) Reduction Reduction can be carried out by chemical reduction or catalytic reduction, and is carried out according to a conventional method. Suitable reducing agents used for chemical reduction are
Metals (eg, tin, zinc, iron, etc.) or metal compounds (eg, chromium chloride, chromium acetate, etc.) and organic or inorganic acids (eg, formic acid, acetic acid, propionic acid, trifluoroacetic acid, p-toluenesulfonic acid, Hydrochloric acid, hydrobromic acid, etc.). Suitable catalysts used for catalytic reduction include platinum catalysts (eg, platinum plate, spongy platinum, platinum black, platinum colloid, platinum oxide, platinum wire, etc.), palladium catalysts (eg, spongy palladium, palladium black, oxidized Palladium, palladium charcoal, palladium colloid, palladium / barium sulfate, palladium / barium carbonate, etc.) nickel catalyst (eg, reduced nickel, nickel oxide, Raney nickel, etc.), cobalt catalyst (eg, reduced cobalt, Raney cobalt, etc.), iron catalyst (Eg, reduced iron,
And conventional copper catalysts (eg, reduced copper, Raney copper, Ullman copper, etc.). Reduction is usually
The reaction is carried out in a conventional solvent that does not adversely influence the reaction, and includes water, methanol, ethanol, propanol, N, N-dimethylformamide, tetrahydrofuran, or a mixture thereof. further,
When the above-mentioned acid used in the chemical reduction is in a liquid state, the acid can also be used as a solvent. The reaction temperature of this reduction reaction is not particularly limited, and the reaction is usually performed under cooling to heating.

The method for producing the starting compound (II) will be described below. Method A- Compound (IV) can be produced by introducing a hydroxyl-protecting group into compound (III). This reaction is described in Production Example 1
-It can be carried out by the method described in (1) or a method similar thereto.

Method A-- Compound (VI) can be produced by reacting compound (IV) with compound (V). This reaction was carried out in Production Example 1-
The method can be performed by the method described in (2) or a method similar thereto.

Method A-- Compound (VII) can be produced by reducing compound (VI). This reaction can be carried out by the method described in Production Example 1- (3) or a method analogous thereto.

Method A-- Compound (VIII) can be produced by subjecting compound (VII) to an elimination reaction of a protecting group for a hydroxyl group. This reaction can be carried out by the method described in Production Example 1- (4) or a method analogous thereto.

Method A-- Compound (X) is prepared by converting compound (VIII) to compound (IX)
Can be produced by reacting This reaction can be carried out by the method described in Production Example 1- (5) or a method analogous thereto.

Method A-- Compound (XII) can be produced by reacting compound (X) with compound (XI). This reaction is described in Production Example 2
The method can be performed by the method described in 7- (5) or a method similar thereto.

Method A-- Compound (XIII) can be produced by subjecting compound (XII) to halogenation. This reaction was carried out according to Production Example 19-
The method can be performed by the method described in (4) or a method similar thereto.

Method A-- Compound (IIa) or a salt thereof is compound (XIII)
By reacting with a compound (XIV) or a salt thereof. This reaction can be carried out by the method described in Production Example 1- (7) or a method analogous thereto.

Method B-- Compound (XVI) was prepared by converting compound (XV) to compound (XI)
Can be produced by reacting This reaction can be carried out by the method described in Production Example 27- (5) or a method analogous thereto.

Method B-- Compound (XVII) can be produced by subjecting compound (XVI) to halogenation. This reaction was carried out according to Production Example 19-
The method can be performed by the method described in (4) or a method similar thereto.

Method B-- Compound (XVIII) or a salt thereof can be prepared by reacting compound (XVI)
It can be produced by reacting I) with compound (XIV) or a salt thereof. This reaction can be carried out by the method described in Production Example 1- (7) or a method analogous thereto.

Method B-- Compound (IIb) or a salt thereof can be prepared by reacting compound (XVII)
It can be produced by reacting I) or a salt thereof with compound (XIX). This reaction can be carried out by the method described in Production Example 40- (4) or a method analogous thereto.

Method C-- Compound (XXI) can be produced by introducing a hydroxyl-protecting group into compound (XX). This reaction is described in Production Example 1
-It can be carried out by the method described in (1) or a method similar thereto.

Method C-- Compound (XXIII) can be produced by reacting compound (XXI) with compound (XXII). This reaction can be carried out by the method described in Production Example 3- (2) or a method analogous thereto.

Method C-- Compound (XXIV) can be produced by subjecting compound (XXIII) to an elimination reaction of a protecting group for a hydroxyl group. This reaction can be carried out by the method described in Production Example 1- (4) or a method analogous thereto.

Method C-- Compound (XXV) can be produced by subjecting compound (XXIV) to halogenation. This reaction is described in Production Example 3-
The method can be performed by the method described in (4) or a method similar thereto.

Method C-- Compound (XXVII) or a salt thereof can be prepared by reacting compound (XX)
V) with compound (XXVI) or a salt thereof. This reaction can be carried out by the method described in Production Example 3- (5) or a method analogous thereto.

Method C-- Compound (IIc) or a salt thereof can be prepared by reacting compound (XXVI)
It can be produced by reacting I) or a salt thereof with compound (XXVIII) or a salt thereof. This reaction can be carried out by the method described in Production Example 3- (6) or a method analogous thereto.

The novel 2-amino-1,3-propanediol derivative (I) and a pharmaceutically acceptable salt thereof have pharmacological activities such as immunosuppressive activity, and can be used for heart, kidney, liver, bone marrow, Skin, cornea, lung, pancreas, small intestine, limbs,
Rejection by transplantation of organs or tissues such as muscles and nerves; graft-versus-host disease by bone marrow transplantation; rheumatoid arthritis, systemic lupus erythematosus, Hashimoto's thyroiditis, multiple sclerosis,
It is useful for treating or preventing autoimmune diseases such as myasthenia gravis, type I diabetes, and immune-related diseases such as psoriasis.

In addition, compound (I) and its pharmaceutically acceptable salts are also useful, for example, for psoriasis, atopic dermatitis, contact dermatitis, further eczema dermatitis, seborrheic dermatitis,
Lichen planus, pemphigus, bullous pemphigoid, epidermolysis bullosa, urticaria, angioedema, vasculitis, erythema, cutaneous eosinophilia,
Expression of inflammatory and hyperproliferative skin diseases such as lupus erythematosus, acne, alopecia areata and immunologically related diseases on the skin; various eye diseases such as autoimmune diseases (eg, keratoconjunctivitis, spring catarrh, Uveitis, keratitis, herpetic keratitis, keratoconus, corneal epithelial dystrophy, Bethet's disease-related keratoderma, ocular pemphigus (scarring conjunctivitis), Mohren's ulcer, scleritis, Graves' eye disorder, Vogt-Koyanagi-Harada syndrome, sarcoidosis, etc.); asthma (eg, bronchial asthma, allergic asthma, endogenous asthma, extrinsic asthma, dust asthma), especially chronic or refractory asthma (eg, delayed asthma, airway hyperreactivity) ), Reversible obstructive airway disease, including conditions such as bronchitis; gastric ulcer, vascular injury from ischemic disease, and mucosal and vascular inflammation such as thrombosis, ischemic bowel disease Inflammatory bowel disease, necrotizing enterocolitis, burns associated intestinal lesions, leukotriene B ₄ mediated diseases; Celiac disease, proctitis, eosinophilic gastroenteritis, mastocytosis, as Crohn's disease and ulcerative colitis Intestinal inflammation / allergy; food-related allergic diseases with manifestations away from the gastrointestinal tract, such as migraine, rhinitis and eczema; interstitial nephritis, Goodpasture's syndrome, hemolytic uremic syndrome,
Renal diseases such as diabetic nephropathy; neurological diseases such as polymyositis, Guillain-Barre syndrome, Meniere's disease, polyneuritis, mononeuritis and radiculopathy; endocrine diseases such as hyperthyroidism and Graves'disease; Hematological disorders such as blastic fistula, aplastic anemia, hypoplastic anemia, idiopathic thrombocytopenic purpura, autoimmune hemolytic anemia, granulocytopenia, pernicious anemia, megaloblastic anemia, and erythropoiesis hypoplasia Bone diseases such as osteoporosis; respiratory diseases such as sarcoidosis, pulmonary fibrosis and idiopathic interstitial pneumonia; skin diseases such as dermatomyositis, vitiligo vulgaris, ichthyosis vulgaris, photoallergic sensitivity, and cutaneous T-cell lymphoma;
Cardiovascular diseases such as arteriosclerosis, atherosclerosis, aortic syndrome, polyarteritis nodosa, cardiomyopathy (eg, autoimmune myocarditis, viral myocarditis); scleroderma, Wegener's granulomas Collagen disease such as Sjogren's syndrome; steatosis; eosinophilic fasciosis; periodontal disease such as gingival, periodontal tissue, alveolar bone, and cementum lesions; nephrotic syndrome such as glomerulonephritis; androgenetic alopecia Or senile alopecia;
Muscular dystrophy; pyoderma and Sezary syndrome; Addison's disease; organs (eg, heart, liver, kidney, gastrointestinal tract) that occur during a reactive oxygen-related disease (eg, storage, transplantation or ischemic disease (eg, thrombosis, myocardial infarction)) Organ damage such as ischemic reperfusion injury of the intestine; intestinal diseases such as endotoxin shock, pseudomembranous enteritis, colitis due to drugs or radiation;
Renal diseases such as ischemic acute renal failure and chronic renal failure; poisoning due to pulmonary oxygen or drugs (eg, paraquat, bleomycin), lung diseases such as lung cancer and emphysema; cataract, siderolysis, retinitis pigmentosa, senile macular degeneration Ocular diseases, such as vitreous scar, corneal alkaline burn, erythema multiforme,
Dermatitis such as linear IgA bullous dermatitis and cement dermatitis; and gingivitis, periodontitis, sepsis, pancreatitis, diseases due to environmental pollution (eg, air pollution), aging, carcinogenesis, cancer metastasis, altitude sickness, etc. Other diseases]; diseases due to histamine or leukotriene C ₄ release; Behcet's disease, such as intestinal, vascular or nervous Behcet's disease, and in the oral cavity, skin, eyes, vulva, joints, epididymis, lung, kidney, etc. Useful for treatment and prevention of affecting Behcet's disease.

Furthermore, compound (I) and pharmaceutically acceptable salts thereof may have liver regeneration activity and / or activity to stimulate hepatocyte hypertrophy and proliferation. Therefore,
Compound (I) and pharmaceutically acceptable salts thereof are immunogenic diseases (eg, chronic autoimmune liver diseases such as the group consisting of autoimmune hepatitis, primary biliary cirrhosis and sclerosing cholangitis), Partial hepatectomy, acute liver necrosis (eg, necrosis due to toxins, viral hepatitis, shock or anoxia), viral hepatitis B, non-A / non-B hepatitis, cirrhosis,
And is useful in the treatment and prevention of hepatic failure such as fulminant hepatic failure, delayed-onset hepatic failure and acute aggression of hepatic failure ("acute-on-chronic" liver failure) .

Furthermore, Compound (I) and its pharmaceutically acceptable salts have various useful pharmaceutical activities such as activity for enhancing chemotherapeutic effect, activity for treating or preventing cytomegalovirus infection, and anti-inflammatory activity. May be useful for diseases.

In order to show the usefulness of the target compound (I) and its pharmaceutically acceptable salts, pharmacological test data of representative compounds of the present invention are shown below.

Test compound (a) 2-amino-2- [2- [4- [4- (dimethylphenylsilyl) butoxy] phenyl] ethyl] -1,
3-propanediol hydrochloride (the target compound of Example 44- (2)) (b) 2-amino-2- [2- [4- [5- (trimethylsilyl) pentyloxy] phenyl] ethyl] -1,
3-propanediol hydrochloride (the target compound of Example 29- (2))

Test A (Reduction of Mouse Peripheral Lymphocytes) Test compounds were intraperitoneally administered to 5-week-old male mice. 24
After time, the mice were anesthetized by intraperitoneal administration of 7.5 mg / mouse of pentobarbital. Peripheral blood was collected from the right ventricle with a heparinized syringe. Automatic blood cell analyzer,
Percentage of lymphocytes and granulocytes in peripheral blood was analyzed by Celltacα (Nihon Kohden). The decrease (%) in the number of lymphocytes was calculated by the following equation.

[0081]

(Equation 1)

Test results

[0083]

[Table 1]

Test B (Elongation Effect of Engraftment on Rat Skin Allograft) An 8-week-old male WKAH rat full-thickness ear skin graft was implanted into the lateral rib cage of an 8-week-old male Fischer rat and covered with sterile gauze. The entire chest was wrapped with an elastic bandage. The day of transplantation was designated as day 0. On day 5, the bandages were removed and the implants were observed daily until rejection occurred (defined as when more than 90% of the implants were necrotic). 14 days from the date of transplant,
Test compounds were administered orally daily.

Test results

[0086]

[Table 2]

The pharmaceutical composition of the present invention comprises the desired compound (I)
Or a pharmaceutically acceptable salt thereof as an active ingredient, for rectal administration, pulmonary inhalation (inhalation through the nose or buccal), nasal drops, eye drops, topical (topical administration), oral or parenteral (subcutaneous, intravenous and intramuscular) For example, solid, semi-solid or liquid pharmaceutical preparations containing as a mixture with organic or inorganic carriers or excipients suitable for administration or inhalation or intravesical administration. The active ingredients include, for example, tablets, pellets, troches, capsules, suppositories, creams, ointments, aerosols, powders for inhalation,
It can be mixed with conventional non-toxic pharmaceutically acceptable carriers used in solutions, emulsions, suspensions and any other forms suitable for use. If necessary, auxiliary agents, stabilizers, thickeners, coloring agents, fragrances and the like can be used. The target compound (I) or a pharmaceutically acceptable salt thereof is contained in the pharmaceutical composition in an amount sufficient to exert a desired effect on the course or symptoms of a disease.

For the application of the composition to humans or animals, it is preferred to apply it intravenously, intramuscularly, pulmonary or orally or by inhalation. The therapeutically effective dose of the compound of interest (I) will depend on the age and symptoms of each individual patient to be treated and will depend on them,
In general, a daily dose of 0.01 to 20 mg of the target compound (I) per kg of human or animal body weight is given for intravenous administration, and a human or animal body weight k is given for intramuscular administration.
The daily dose of 0.1 to 20 mg of the target compound (I) per gram, and in the case of oral administration, the daily dose of 0.5 to 50 mg of the target compound (I) per kg of human or animal body weight,
It is administered for the prevention and / or treatment of the above-mentioned diseases.

Further, the desired compound (I) of the present invention or a pharmaceutically acceptable salt thereof is cyclosporine, azathioprine, steroids or tacrolimu
It can also be used in combination with other immunosuppressants such as s).

[0090]

The present invention will be described in more detail with reference to the following production examples and examples. Production Example 1 (1) 10-undecin-1-ol (10 g), 3,
A mixture of 4-dihydro-2H-pyran (7.5 g) and pyridinium p-toluenesulfonate (747 mg) in dichloromethane (200 ml) was stirred at room temperature for 18 hours. The solvent was distilled off, and the residue was purified by a silica gel column (hexane-ethyl acetate, 85:15) to give 2- (10
-Undecinyloxy) tetrahydropyran (11.8
g) was obtained as a colorless oil. NMR (CDCl ₃ , δ): 1.2-1.9 (20H, m), 1.92 (1
(H, t, J = 3Hz), 2.18 (2H, m), 3.38 (1H, m), 3.49 (1H, m),
3.72 (1H, m), 3.87 (1H, m), 4.57 (1H, m)

(2) 2- (10-Undecynyloxy) tetrahydropyran (11.8 g) in tetrahydrofuran (70 ml) was treated with butyllithium (32 ml, 1.6 M solution in hexane) and chlorotrimethylsilane (6.53 ml). ) At -60 ° C. The reaction mixture was warmed to room temperature and stirring continued for 2 hours. An aqueous ammonium chloride solution was added to the mixture, and the resulting mixture was extracted twice with ethyl acetate. The combined organic solution was washed with brine, dried over magnesium sulfate and concentrated to 2-
[11- (Trimethylsilyl) -10-undecynyloxy] tetrahydropyran (12.1 g) was obtained as a colorless oil. NMR (CDCl ₃ , δ): 0.14 (9H, s), 1.2-1.9 (20
H, m), 2.20 (2H, t, J = 7Hz), 3.37 (1H, m), 3.49 (1H, m),
3.72 (1H, m), 3.87 (1H, m), 4.58 (1H, m)

(3) 2- [11- (trimethylsilyl)
-10-undecynyloxy] tetrahydropyran (1
A solution of 2.0 g) in ethanol (120 ml) was treated with 10% palladium on charcoal (1.2 g). The mixture was shaken under hydrogen (3 atm) for 1.5 hours. The catalyst was removed by filtration and the solvent was distilled off to give 2- [11- (trimethylsilyl) undecyloxy] tetrahydropyran (11.4).
g) was obtained as a colorless oil. NMR (CDCl ₃ , δ): -0.04 (9H, s), 0.47 (2H,
m), 1.2-1.9 (22H, m), 3.38 (1H, m), 3.50 (1H, m), 3.7
3 (1H, m), 3.87 (1H, m), 4.58 (1H, m)

(4) 2- [11- (trimethylsilyl)
Undecyloxy] tetrahydropyran (11.4 g)
And pyridinium p-toluenesulfonate (436 m
The mixture of g) in ethanol (100 ml) was stirred at 55 ° C. for 5 hours. The reaction mixture was concentrated, and the residue was purified by a silica gel column (hexane-ethyl acetate, 9: 1) to obtain 11- (trimethylsilyl) -1-undecanol (6.46 g) as a colorless oil. NMR (CDCl ₃ , δ): -0.03 (9H, s), 0.48 (2H,
m), 1.2-1.45 (16H, m), 1.57 (2H, m), 3.64 (2H, q, J = 7H
z)

(5) 11- (trimethylsilyl) -1-
A mixture of undecanol (6.45 g) and triethylamine (4.41 ml) in dichloromethane (150 ml) was treated with methanesulfonyl chloride (2.45 ml).
At 0 ° C. The reaction mixture was stirred at 0 ° C. for 1 hour, washed sequentially with dilute hydrochloric acid and brine, dried over magnesium sulfate, and concentrated to give 11- (trimethylsilyl) undecyl methanesulfonate (9.73 g) as a colorless oil. Was. NMR (CDCl ₃ , δ): -0.03 (9H, s), 0.47 (2H,
t, J = 7Hz), 1.2-1.45 (16H, m), 1.75 (2H, m), 3.00 (3H,
s), 4.22 (2H, t, J = 7Hz)

(6) A solution of 11- (trimethylsilyl) undecyl methanesulfonate (8.5 g) in 2-butanone (140 ml) was treated with sodium iodide (4.74 g).
And the mixture was refluxed for 3 hours. Concentrate the mixture,
Poured into ice water and the resulting mixture was extracted twice with ethyl acetate. The combined organic solution was washed with brine, dried over magnesium sulfate and concentrated. The residue was purified by a silica gel column (hexane as an eluent) to obtain 11- (trimethylsilyl) undecyl iodide (8.5 g) as a colorless oil. NMR (CDCl ₃ , δ): -0.04 (9H, s), 0.47 (2H,
t, J = 7Hz), 1.2-1.45 (8H, m), 1.81 (2H, m), 3.18 (2H,
(t, J = 7Hz)

(7) Sodium (1.63 g) was dissolved in ethanol (60 ml), and diethyl acetamidomalonate (15.4 g) was added to the solution. To the obtained solution, a solution of 11- (trimethylsilyl) undecyl iodide (8.40 g) in tetrahydrofuran (50 ml) was added dropwise, and the mixture was stirred at 75 ° C. for 5 hours. The mixture was concentrated, poured into ice water, and the resulting mixture was extracted twice with ethyl acetate. The combined organic solution was washed with brine, dried over magnesium sulfate and concentrated. The residue was purified on a silica gel column (hexane-ethyl acetate, 3: 1) to give 2
Diethyl -acetamido-2- [11- (trimethylsilyl) undecyl] malonate (9.1 g) was obtained as a colorless oil. NMR (CDCl ₃ , δ): -0.04 (9H, s), 0.44 (2H,
m), 1.08 (2H, m), 1.2-1.35 (22H, m), 2.04 (3H, s), 2.
31 (2H, m), 4.24 (4H, q, J = 7Hz), 6.76 (1H, s)

Example 1 (1) A solution of diethyl 2-acetamido-2- [11- (trimethylsilyl) undecyl] malonate (9.1 g) in tetrahydrofuran (150 ml) was placed in an ice bath with lithium borohydride (3.57 g). ) And the mixture was stirred at room temperature for 23 hours. Excess reagent was quenched with 0.5N hydrochloric acid and the resulting mixture was extracted twice with ethyl acetate.
The combined organic solution was washed with brine, dried over magnesium sulfate and concentrated. The residue was purified on a silica gel column (ethyl acetate as eluent) to give 2-acetamido-2-
[11- (trimethylsilyl) undecyl] -1,3-
Propanediol (3.28 g) was obtained as a solid. NMR (DMSO-d ₆ , δ): -0.03 (9H, s), 0.47
(2H, t, J = 7Hz), 1.2-1.35 (18H, m), 1.49 (2H, m), 3.44
(3H, m), 5.29 (2H, s), 7.76 (3H, s)

(2) 2-acetamido-2- [11-
A mixture of (trimethylsilyl) undecyl] -1,3-propanediol (3.0 g) in methanol (40 ml) -water (40 ml) was treated with lithium hydroxide monohydrate (1.75 g), and the mixture was treated with 30%. Reflux for minutes.
The mixture was concentrated and extracted twice with ethyl acetate. The combined organic solution was washed with brine, dried over magnesium sulfate and concentrated. The residue was dissolved in ethanol, and 4N hydrogen chloride (1,4-dioxane solution, 5.0 ml) was added to this solution.
Was added. The solvent was distilled off, and the residue was crystallized from ethyl acetate to give 2-amino-2- [11- (trimethylsilyl) undecyl] -1,3-propanediol hydrochloride (2.7).
0 g). NMR (DMSO-d ₆ , δ): -0.03 (9H, s), 0.47
(2H, m), 1.2-1.35 (18H, m), 1.49 (2H, m), 3.44 (4H,
m), 5.29 (2H, br s), 7.76 (3H, br s)

Production Example 2 (1) In the same manner as in Production Example 1- (2), 3- (ter)
From 3-tert-butyldimethylsilyloxy) -1-propyne and chlorodimethyloctylsilane, 3- (tert-
(Butyldimethylsilyloxy) -1- (dimethyloctylsilyl) -1-propyne was obtained. NMR (CDCl ₃ , δ): 0.12 (12H, s), 0.59 (2H,
m), 0.8-0.9 (12H, m), 1.2-1.4 (12H, m), 4.30 (2H, s)

(2) In the same manner as in Production Example 1- (3),
3- (tert-butyldimethylsilyloxy) -1-
(Dimethyloctylsilyl) -1-propyne to 1-
(Tert-Butyldimethylsilyloxy) -3- (dimethyloctylsilyl) propane was obtained. NMR (CDCl ₃ , δ): -0.04 (6H, s), 0.06 (6H,
s), 0.4-0.55 (4H, m), 0.85-0.95 (12H, m), 1.2-1.35
(12H, m), 1.4-1.55 (2H, m), 3.54 (2H, t, J = 7Hz)

(3) 1- (tert-butyldimethylsilyloxy) -3- (dimethyloctylsilyl) propane (14.2 g) in tetrahydrofuran (100 ml)
The solution was treated with tetrabutylammonium fluoride (45.3 ml of a 1.0 M solution in tetrahydrofuran).
The reaction mixture was stirred at room temperature for 2 hours and concentrated. The residue was dissolved in ethyl acetate, washed with brine, dried over magnesium sulfate, and the solvent was distilled off. The residue was purified on a silica gel column (hexane-ethyl acetate, 85:15) to give 3-
(Dimethyloctylsilyl) -1-propanol (8.
81g) was obtained as a colorless oil. NMR (CDCl ₃ , δ): -0.03 (6H, s), 0.45-0.55
(4H, m), 0.88 (3H, t, J = 7Hz), 1.2-1.35 (12H, m), 1.55
(2H, m), 3.61 (2H, q, J = 7Hz)

(4) In the same manner as in Production Example 1- (5),
3- (dimethyloctylsilyl) propyl methanesulfonate was obtained from 3- (dimethyloctylsilyl) -1-propanol and methanesulfonyl chloride. NMR (CDCl ₃ , δ): -0.02 (6H, s), 0.45-0.6
(4H, m), 0.88 (3H, t, J = 7Hz), 1.2-1.35 (12H, m), 1.73
(2H, m), 3.00 (3H, s), 4.27 (2H, t, J = 7Hz)

(5) In the same manner as in Production Example 1- (6),
3- (Dimethyloctylsilyl) propyl iodide was obtained from 3- (dimethyloctylsilyl) propyl methanesulfonate. NMR (CDCl ₃ , δ): -0.03 (6H, s), 0.45-0.65
(4H, m), 0.88 (3H, t, J = 7Hz), 1.2-1.35 (12H, m), 1.82
(2H, m), 3.18 (2H, t, J = 7Hz)

(6) In the same manner as in Production Example 1- (7),
From 3- (dimethyloctylsilyl) propyl iodide and diethyl acetamidomalonate to 2-acetamido-2- [3- (dimethyloctylsilyl) propyl]
Diethyl malonate was obtained. NMR (CDCl ₃ , δ): -0.08 (6H, s), 0.4-0.55
(4H, m), 0.89 (3H, t, J = 7Hz), 1.05-1.35 (20H, m), 2.03
(3H, s), 2.34 (2H, m), 4.34 (4H, q, J = 7Hz), 6.77 (1H,
s)

Example 2 (1) In the same manner as in Example 1- (1), diethyl 2-acetamido-2- [3- (dimethyloctylsilyl) propyl] malonate was used to give 2-acetamido-2- [3
-(Dimethyloctylsilyl) propyl] -1,3-propanediol was obtained. NMR (CDCl ₃ , δ): -0.04 (6H, s), 0.4-0.55
(4H, m), 0.88 (3H, t, J = 7Hz), 0.2-0.35 (12H, m), 1.62
(2H, m), 2.05 (3H, s), 3.58 (2H, m), 3.75-3.9 (4H, m),
5.82 (1H, s)

(2) In the same manner as in Example 1- (2),
From 2-acetamido-2- [3- (dimethyloctylsilyl) propyl] -1,3-propanediol to 2-amino-2- [3- (dimethyloctylsilyl) propyl] -1,3-propanediol hydrochloride Obtained. NMR (DMSO-d ₆ , δ): -0.03 (6H, s), 0.4-0.
55 (4H, m), 0.87 (3H, t, J = 7Hz), 1.2-1.35 (14H, m), 1.
55 (2H, m), 3.45 (4H, m), 5.31 (2H, t, J = 5Hz), 7.75 (3
H, s)

Production Example 3 (1) In the same manner as in Production Example 1- (1), 11-bromo-1-undecanol and 3,4-dihydro-2H-
2- (11-Bromoundecyloxy) tetrahydropyran was obtained from pyran. NMR (CDCl ₃ , δ): 1.25-1.9 (18H, m), 3.39
(3H, m), 3.50 (1H, m), 3.72 (1H, m), 3.85 (1H, m), 4.5
6 (1H, m)

(2) To a solution of 2- (11-bromoundecyloxy) tetrahydropyran (5.0 g) in dry tetrahydrofuran, under N ₂ gas, 1.5 M trimethylsilylmethylmagnesium chloride (tetrahydrofuran solution, 22.4 ml) and 0.1 M dilithium tetrachlorocuprate (tetrahydrofuran solution, 1.49 ml)
Was added. The mixture was stirred overnight and a saturated ammonium chloride solution was added. The organic layer was separated, dried and concentrated.
The crude residue was chromatographed on a silica gel column (50 g, hexane-ethyl acetate, 10: 1 as eluent) to give 2- [12- (trimethylsilyl) dodecyloxy] tetrahydropyran (4.7 g) as an oil. . NMR (CDCl ₃ , δ): -0.03 (9H, s), 0.50 (2H,
m), 1.25-1.95 (26H, m), 3.42 (1H, m), 3.53 (1H, m), 3.
77 (1H, m), 3.90 (1H, m), 4.62 (1H, m)

(3) In the same manner as in Production Example 1- (4),
12- (Trimethylsilyl) -1-dodecanol was obtained from 2- (11-bromoundecyloxy) tetrahydropyran. NMR (CDCl ₃ , δ): -0.02 (9H, s), 0.50 (2H,
m), 1.31 (19H, m), 1.60 (2H, m), 3.67 (2H, dt, J = 7,7Hz)

(4) 12- (trimethylsilyl) -1-
Dodecanol (2.9 g), tetrabromomethane (5.
59 g) and triphenylphosphine (4.42 g)
In chloroform (60 ml) was stirred overnight. After evaporating the solvent, the crude residue was extracted with ether.
The ether extract was concentrated and concentrated on a silica gel column (50
g, hexane-ethyl acetate (10: 1) as eluent to give 1-bromo-12- (trimethylsilyl) dodecane (2.2 g) as an oil. NMR (CDCl ₃ , δ): -0.02 (9H, s), 0.50 (2H,
m), 1.30 (16H, m), 1.45 (2H, m), 1.88 (2H, t, J = 7Hz),
3.43 (2H, t, J = 7Hz)

(5) To a solution of sodium ethoxide prepared from sodium (0.4 g) in dry ethanol (22 ml) was added diethyl malonate (2.75 g),
Then 1-bromo-12- (trimethylsilyl) dodecane (2.2 g) was added. The mixture was stirred under reflux overnight. The cooled reaction solution was acidified with 1N hydrochloric acid, diluted with water and extracted with ethyl acetate. The combined extracts were washed with brine, dried over magnesium sulfate and evaporated. The crude residue was chromatographed on a silica gel column (40 g, hexane-ethyl acetate, 10: 1 as eluent) to give diethyl 2- [12- (trimethylsilyl) dodecyl] malonate (1.9 g) as an oil. . NMR (CDCl ₃ , δ): -0.02 (9H, s), 0.50 (2H,
m), 1.31 (26H, m), 1.90 (2H, m), 3.34 (1H, t, J = 7Hz),
4.22 (4H, q, J = 7Hz)

(6) Sodium hydride (60%, 0.21 g) was added to a stirred solution of diethyl 2- [12- (trimethylsilyl) dodecyl] malonate (1.9 g) in dry N, N-dimethylformamide (20 ml). ) Was added and the mixture was stirred for 2 hours. O- (2,4-dinitrophenyl) hydroxylamine (1.04 g) was added and stirring continued for another 10 minutes. The reaction mixture was washed with water (60 ml)
And extracted with ethyl acetate (20 ml × 3). The combined extracts were washed sequentially with water and brine, and dried over magnesium sulfate. After evaporating the solvent, the crude residue was chromatographed on a silica gel column (30 g, eluant: hexane-ethyl acetate, 4: 1) to give diethyl 2-amino-2- [12- (trimethylsilyl) dodecyl] malonate. (1.7 g) was obtained as an oil. NMR (CDCl ₃ , δ): -0.03 (9H, s), 0.50 (2H,
m), 1.30 (24H, m), 1.95 (2H, m), 2.00 (2H, m), 4.25 (4
(H, q, J = 7Hz)

Example 3 In the same manner as in Example 1- (1), 2-amino-2-
2-Amino-2- [12- (trimethylsilyl) dodecyl] -1,3-propanediol hydrochloride was obtained from diethyl [12- (trimethylsilyl) dodecyl] malonate. NMR (DMSO-d ₆ , δ): 0.50 (2H, m), 1.29 (2
0H, m), 1.52 (2H, m), 3.46 (4H, m), 5.31 (2H, m), 7.75
(3H, br s)

Production Example 4 (1) In the same manner as in Production Example 1- (1), 8- (2-tetrahydropyranyloxy)-was prepared from 1,8-octanediol and 3,4-dihydro-2H-pyran. 1-octanol was obtained. NMR (CDCl ₃ , δ): 1.2-1.9 (18H, m), 3.38 (1
H, m), 3.50 (1H, m), 3.63 (2H, m), 3.72 (1H, m), 3.88
(1H, m), 4.57 (1H, m)

(2) A mixture of 8- (2-tetrahydropyranyloxy) -1-octanol (4.27 g) and pyridine (3 ml) in dichloromethane (15 ml) was treated with p-toluenesulfonyl chloride (3.89 g). Upon treatment, the mixture was stirred at room temperature for 15 hours. The mixture was concentrated, poured into ice water, and the resulting mixture was extracted twice with ethyl acetate. Wash the combined organic solution with saline,
Dried over magnesium sulfate and concentrated. The residue was purified by a silica gel column (hexane-ethyl acetate, 85:15) to give 8-[(2-tetrahydropyranyl) oxy] octyl p-toluenesulfonate (5.19 g) as a colorless oil. NMR (CDCl ₃ , δ): 1.2-1.9 (18H, m), 2.46 (3
H, s), 3.38 (1H, m), 3.51 (1H, m), 3.72 (1H, m), 3.88
(1H, m), 4.02 (2H, t, J = 7Hz), 7.36 (2H, d, J = 8Hz), 7.80
(2H, d, J = 8Hz)

(3) In the same manner as in Production Example 3- (2),
2- [9- (Trimethylsilyl) nonyloxy] tetrohydropyran was obtained from 8-[(2-tetrahydropyranyl) oxy] octyl p-toluenesulfonate and trimethylsilylmagnesium chloride. NMR (CDCl ₃ , δ): -0.03 (9H, s), 0.47 (2H,
m), 1.25-1.9 (20H, m), 3.38 (1H, m), 3.49 (1H, m), 3.
74 (1H, m), 3.87 (1H, m), 4.57 (1H, m)

(4) In the same manner as in Production Example 1- (4),
9- (Trimethylsilyl) -1-nonanol was obtained from 2- [9- (trimethylsilyl) nonyloxy] tetrohydropyran. NMR (CDCl ₃ , δ): -0.03 (9H, s), 0.47 (2H,
t, J = 7Hz), 1.2-1.4 (13H, m), 1.57 (2H, m), 3.65 (2H,
m)

(5) 9 in the same manner as in Production Example 3- (4)
1-Bromo-9- (trimethylsilyl) nonane was obtained from-(trimethylsilyl) -1-nonanol. NMR (CDCl ₃ , δ): -0.03 (9H, s), 0.47 (2H,
t, J = 7Hz), 1.25-1.35 (10H, m), 1.43 (2H, m), 1.86 (2
H, m), 3.41 (2H, t, J = 7Hz)

(6) 1 was prepared in the same manner as in Production Example 1- (7).
2-acetamido-2-from -bromo-9- (trimethylsilyl) nonane and diethyl acetamidomalonate
Diethyl [9- (trimethylsilyl) nonyl] malonate was obtained. NMR (CDCl ₃ , δ): -0.03 (9H, s), 0.47 (2H,
t, J = 7Hz), 1.09 (2H, m), 1.2-1.35 (18H, m), 2.05 (3H, m
s), 2.31 (2H, m), 4.25 (4H, q, J = 7Hz), 6.77 (1H, s)

Example 4 (1) In the same manner as in Example 1- (1), diethyl 2-acetamido-2- [9- (trimethylsilyl) nonyl] malonate was converted to diethyl 2-acetamido-2- [9- ( [Trimethylsilyl) nonyl] -1,3-propanediol was obtained. NMR (CDCl ₃ , δ): -0.03 (9H, s), 0.47 (2H,
m), 1.2-1.35 (14H, m), 1.59 (2H, m), 2.05 (3H, s), 3.
57 (2H, m), 3.82 (4H, m), 5.83 (1H, s)

(2) In the same manner as in Example 1- (2),
2-acetamido-2- [9- (trimethylsilyl) nonyl] -1,3-propanediol to 2-amino-2
-[9- (Trimethylsilyl) nonyl] -1,3-propanediol hydrochloride was obtained. NMR (DMSO-d ₆ , δ): -0.03 (9H, s), 0.47
(2H, m), 1.15-1.35 (14H, m), 1.49 (2H, m), 3.43 (4H,
m), 5.29 (2H, t, J = 5Hz), 7.75 (3H, s)

Production Example 5 (1) In the same manner as in Production Example 1- (1), 2- (12-bromododecyloxy) tetrahydrofuran was prepared from 12-bromo-1-dodecanol and 3,4-dihydro-2H-pyran. I got Piran. NMR (CDCl ₃ , δ): 1.2-1.9 (26H, m), 3.35-3.
55 (4H, m), 3.73 (1H, m), 3.88 (1H, m), 4.58 (1H, m)

(2) In the same manner as in Production Example 3- (2),
From 2- (12-bromododecyloxy) tetrahydropyran and trimethylsilylmagnesium chloride to 2- [13- (trimethylsilyl) tridecyloxy]
Tetrahydropyran was obtained. NMR (CDCl ₃ , δ): -0.03 (9H, s), 0.47 (2H,
m), 1.2-1.9 (28H, m), 3.38 (1H, m), 3.50 (1H, m), 3.7
3 (1H, m), 3.87 (1H, m), 4.57 (1H, m)

(3) In the same manner as in Production Example 1- (4),
2- [13- (trimethylsilyl) tridecyloxy]
13- (trimethylsilyl)-from tetrahydropyran
1-Tridecanol was obtained. NMR (CDCl ₃ , δ): -0.03 (9H, s), 0.47 (2H,
m), 1.2-1.4 (21H, m), 1.57 (2H, m), 3.64 (2H, m)

(4) In the same manner as in Production Example 3- (4),
1-Bromo-13- (trimethylsilyl) tridecane was obtained from 13- (trimethylsilyl) -1-tridecanol. NMR (CDCl ₃ , δ): -0.03 (9H, s), 0.47 (2H,
t, J = 7Hz), 1.2-1.35 (18H, m), 1.42 (2H, m), 1.86 (2H,
m), 3.41 (2H, t, J = 7Hz)

(5) In the same manner as in Production Example 1- (7),
Diethyl 2-acetamido-2- [13- (trimethylsilyl) tridecyl] malonate was obtained from 1-bromo-13- (trimethylsilyl) tridecane and diethyl acetamidomalonate. NMR (CDCl ₃ , δ): -0.03 (9H, s), 0.47 (2H,
t, J = 7Hz), 1.09 (2H, m), 1.2-1.35 (26H, m), 2.05 (3H, m
s), 2.31 (2H, m), 4.25 (4H, q, J = 7Hz), 6.76 (1H, s)

Example 5 (1) In the same manner as in Example 1- (1), 2-acetamido-2- [13- (trimethylsilyl) tridecyl]
From diethyl malonate to 2-acetamido-2- [13-
(Trimethylsilyl) tridecyl] -1,3-propanediol was obtained. NMR (CDCl ₃ , δ): -0.03 (9H, s), 0.47 (2H,
t, J = 7Hz), 1.2-1.35 (22H, m), 1.58 (2H, m), 2.05 (3H,
s), 3.58 (2H, m), 3.82 (4H, m), 5.82 (1H, s)

(2) In the same manner as in Example 1- (2),
2-acetamido-2- [13- (trimethylsilyl)
Tridecyl] -1,3-propanediol to 2-amino-2- [13- (trimethylsilyl) tridecyl]-
1,3-propanediol hydrochloride was obtained. NMR (DMSO-d ₆ , δ): -0.03 (9H, s), 0.47
(2H, t, J = 7Hz), 1.2-1.35 (22H, m), 1.50 (2H, m), 3.44
(4H, m), 5.29 (2H, t, J = 5Hz), 7.74 (3H, s)

Production Example 6 (1) In the same manner as in Production Example 1- (1), 1,9-nonanediol was converted to 2- (9-hydroxynonanyloxy).
Tetrahydropyran was obtained. NMR (CDCl ₃ , δ): 1.2-1.9 (20H, m), 3.38 (1
H, m), 3.52 (1H, m), 3.6-3.7 (2H, m), 3.74 (1H, m), 3.
88 (1H, m), 4.58 (1H, m) ESI-MS: 245 (M + H)

(2) In the same manner as in Production Example 4- (2),
2- [9- (p-Toluenesulfonyl) nonyloxy] tetrahydropyran was obtained from 2- (9-hydroxynonanyloxy) tetrahydropyran. NMR (CDCl ₃ , δ): 1.15-1.4 (10H, m), 1.45-
1.9 (10H, m), 2.45 (3H, s), 3.38 (1H, m), 3.5 (1H, m),
3.72 (1H, m), 3.86 (1H, m), 4.02 (2H, t, J = 7Hz), 7.35
(2H, d, J = 7Hz), 7.8 (2H, d, J = 7Hz) ESI-MS: 421 (M + Na)

(3) In the same manner as in Production Example 3- (2),
2- [9- (p-toluenesulfonyl) nonyloxy]
2- [10- (Trimethylsilyl) decyloxy] tetrahydropyran was obtained from tetrahydropyran. NMR (CDCl ₃ , δ): -0.04 (9H, s), 0.45 (2H,
m), 1.2-1.35 (14H, m), 1.4-1.85 (8H, m), 3.42 (1H,
m), 3.54 (1H, m), 3.76 (1H, m), 3.9 (1H, m), 4.6 (1H,
m)

(4) In the same manner as in Production Example 1- (4),
2- [10- (trimethylsilyl) decyloxy] tetrahydropyran to 10- (trimethylsilyl) -1-
Decanol was obtained. NMR (CDCl ₃ , δ): -0.04 (9H, s), 0.46 (2H,
m), 1.16-1.4 (14H, m), 1.5-1.6 (2H, m), 1.62 (2H, q, J
= 7Hz)

(5) In the same manner as in Production Example 3- (4),
10- (trimethylsilyl) -1-decanol to 1-
Bromo-10- (trimethylsilyl) decane was obtained. NMR (CDCl ₃ , δ): -0.04 (9H, s), 0.46 (2H,
m), 1.2-1.32 (12H, m), 1.32-1.44 (2H, m), 1.78-1.88
(2H, m), 3.4 (2H, t, J = 7.5Hz)

(6) In the same manner as in Production Example 3- (5),
2 from 1-bromo-10- (trimethylsilyl) decane
-Diethyl [-[10- (trimethylsilyl) decyl] malonate was obtained. NMR (CDCl ₃ , δ): -0.04 (9H, s), 0.46 (2H,
m), 1.16-1.32 (22H, m), 1.8-1.92 (2H, m), 3.3 (1H, t, J
= 7.5Hz), 4.2 (4H, q, J = 7.5Hz) ESI-MS: 373 (M + H)

(7) In the same manner as in Production Example 3- (6),
Diethyl 2- [10- (trimethylsilyl) decyl] malonate and O- (2,4-dinitrophenyl) hydroxylamine gave diethyl 2-amino-2- [10- (trimethylsilyl) decyl] malonate. NMR (CDCl ₃ , δ): -0.04 (9H, s), 0.46 (2H,
m), 1.16-1.32 (22H, m), 1.88-2.0 (4H, m), 4.2 (4H, q, J
= 7.5Hz) ESI-MS: 388 (M + H)

Example 6 In the same manner as in Example 1- (1), 2-amino-2-
[10- (trimethylsilyl) decyl] malonate to 2-amino-2- [10- (trimethylsilyl)
[Decyl] -1,3-propanediol hydrochloride was obtained. NMR (DMSO-d ₆ , δ): -0.04 (9H, s), 0.46
(2H, m), 1.16-1.3 (16H, m), 1.42-1.52 (2H, m), 3.36-
3.5 (4H, m), 5.28 (2H, t, J = 7Hz), 7.7-7.8 (3H, br)

Production Example 7 (1) In the same manner as in Production Example 1- (1), 2- (9-decenyloxy) tetrahydropyran was prepared from 10-decen-1-ol and 3,4-dihydro-2H-pyran. Obtained. NMR (CDCl ₃ , δ): 1.28 (10H, m), 1.55 (6H,
m), 1.72 (1H, m), 1.83 (1H, m), 2.04 (2H, m), 3.38 (1
H, m), 3.50 (1H, m), 3.73 (1H, m), 3.87 (1H, m), 4.58
(1H, m), 4.93 (1H, m), 4.99 (1H, m), 5.81 (1H, m)

(2) A mixture of 2- (9-decenyloxy) tetrahydropyran (2.0 g), dimethylisobutylsilane (1.35 g) and 0.1 M hexachloroplatinic (IV) acid in isopropanol (one drop) was added to 4 Stirred for days. The reaction mixture was applied to a silica gel column (20
g, hexane-ethyl acetate (10: 1) as eluent to give 2- [10- (dimethylisobutylsilyl) decyloxy] tetrahydropyran as an oil. NMR (CDCl ₃ , δ): -0.02 (6H, s), 0.50 (2H,
m), 0.53 (2H, d, J = 7Hz), 0.95 (6H, d, J = 7Hz), 1.25-1.90
(17H, m), 3.40 (1H, m), 3.52 (1H, m), 3.75 (1H, m),
3.90 (1H, m), 4.60 (1H, m)

(3) In the same manner as in Production Example 1- (4),
10- (Dimethylisobutylsilyl) -1-decanol was obtained from 2- [10- (dimethylisobutylsilyl) decyloxy] tetrahydropyran. NMR (CDCl ₃ , δ): -0.02 (6H, s), 0.50 (2H,
m), 0.51 (2H, d, J = 7Hz), 0.95 (6H, d, J = 7Hz), 1.21 (14
H, m), 1.60 (2H, m), 1.79 (1H, m), 3.67 (2H, m)

(4) In the same manner as in Production Example 1- (5),
10- (Dimethylisobutylsilyl) decyl methanesulfonate was obtained from 10- (dimethylisobutylsilyl) -1-decanol. NMR (CDCl ₃ , δ): -0.02 (6H, s), 0.50 (2H,
m), 0.52 (2H, d, J = 7Hz), 0.95 (6H, d, J = 7Hz), 1.25-1.50
(14H, m), 1.80 (3H, m), 3.03 (3H, s), 4.25 (2H, t, J = 7
Hz)

(5) In the same manner as in Production Example 3- (5),
From 2- (10- (dimethylisobutylsilyl) decyl methanesulfonate and diethyl malonate)
Diethyl (dimethylisobutylsilyl) decyl] malonate was obtained. NMR (CDCl ₃ , δ): -0.02 (6H, s), 0.50 (2H,
m), 0.53 (2H, d, J = 7Hz), 0.95 (6H, d, J = 7Hz), 1.30 (22
H, m), 1.78 (1H, m), 1.91 (2H, m), 3.33 (1H, t, J = 7Hz),
4.22 (4H, q, J = 7Hz)

(6) In the same manner as in Production Example 3- (6),
From 2- [10- (dimethylisobutylsilyl) decyl] malonate and O- (2,4-dinitrophenyl) hydroxylamine, 2-amino-2- [10-
Diethyl (dimethylisobutylsilyl) decyl] malonate was obtained. NMR (CDCl ₃ , δ): -0.03 (3H, s), 0.50 (2H,
m), 0.53 (2H, d, J = 7Hz), 0.95 (6H, d, J = 7Hz), 1.30 (22
H, m), 1.60 (2H, m), 1.78 (1H, m), 1.96 (4H, m), 4.25
(4H, q, J = 7Hz)

Example 7 In the same manner as in Example 1- (1), 2-amino-2-
2-Amino-2- [10- (dimethylisobutylsilyl) decyl] -1,3-propanediol hydrochloride was obtained from diethyl [10- (dimethylisobutylsilyl) decyl] malonate. Melting point: 60 ° C. (shrinkage) NMR (CDCl ₃ , δ): −0.03 (6H, s), 0.50 (2H,
m), 0.53 (2H, d, J = 7Hz), 0.95 (6H, d, J = 7Hz), 1.30 (16
H, m), 1.73 (2H, m), 1.78 (1H, m), 3.83 (4H, m), 7.80
(3H, m)

Production Example 8 (1) In the same manner as in Production Example 40- (4), (8-bromooctyl) triethylsilane was obtained from 1-bromo-7-octene and triethylsilane. NMR (CDCl ₃ , δ): 0.45-0.65 (8H, m), 0.85-
1.05 (21H, m), 3.40 (2H, t, J = 7Hz)

(2) In the same manner as in Production Example 3- (5),
Diethyl 2- [8- (triethylsilyl) octyl] malonate was obtained from (8-bromooctyl) triethylsilane and diethyl malonate. NMR (CDCl ₃ , δ): 0.50 (6H, q, J = 7 Hz), 0.90
(2H, m), 0.93 (9H, t, J = 7Hz), 1.30 (18H, m), 1.90 (2H, m
m), 1.98 (2H, m), 3.30 (1H, t, J = 7Hz), 4.20 (4H, q, J = 7
Hz)

(3) In the same manner as in Production Example 3- (6),
Diethyl 2- [8- (triethylsilyl) octyl] malonate and O- (2,4-dinitrophenyl) hydroxylamine gave diethyl 2-amino-2- [8- (triethylsilyl) octyl] malonate. NMR (CDCl ₃ , δ): 0.50 (8H, m), 0.92 (9H, t,
J = 7Hz), 1.28 (18H, m), 1.93 (2H, m), 1.97 (2H, s), 4.2
3 (4H, q, J = 7Hz)

Example 8 In the same manner as in Example 1- (1), 2-amino-2-
2-Amino-2- [8- (triethylsilyl) octyl] -1,3-propanediol hydrochloride was obtained from diethyl [8- (triethylsilyl) octyl] malonate. NMR (CDCl ₃ , δ): 0.48 (2H, m), 0.49 (6H, q,
J = 7Hz), 0.92 (6H, t, J = 7Hz), 1.27 (14H, m), 3.6-3.9
(4H, m)

Production Example 9 (1) In the same manner as in Production Example 40- (4), 2- (9-
Diethyl 2- [10- (cyclohexyldimethylsilyl) decyl] malonate was obtained from diethyl (decenyl) malonate and cyclohexyldimethylsilane. NMR (CDCl ₃ , δ): -0.12 (6H, s), 1.38-1.61
(3H, m), 0.94-1.35 (20H, m), 1.24 (6H, t, J = 7Hz), 1.56
-1.76 (6H, m), 1.80-1.93 (2H, m), 3.29 (1H, t, J = 7Hz),
4.17 (4H, q, J = 7Hz)

(2) In the same manner as in Production Example 3- (6),
From 2- [10- (cyclohexyldimethylsilyl) decyl] malonate and O- (2,4-dinitrophenyl) hydroxylamine to 2-amino-2- [1
Diethyl 0- (cyclohexyldimethylsilyl) decyl] malonate was obtained. NMR (CDCl ₃ , δ): -0.10 (6H, s), 0.42-0.50
(2H, m), 0.58 (1H, m), 1.00-1.36 (20H, m), 1.27 (6H,
(t, J = 7Hz), 1.60-1.77 (6H, m), 1.87-2.02 (4H, m), 4.32
(4H, q, J = 7Hz)

Example 9 In the same manner as in Example 1- (1), 2-amino-2-
2-Amino-2- [10- (cyclohexyldimethylsilyl) decyl] -1,3-propanediol hydrochloride was obtained from diethyl [10- (cyclohexyldimethylsilyl) decyl] malonate. NMR (DMSO-d ₆ , δ): -0.12 (6H, s), 0.39-
0.47 (2H, m), 0.55 (1H, m), 0.95-1.34 (20H, m), 1.41-
1.74 (8H, m), 3.35-3.48 (4H, m), 5.26 (2H, t, J = 5Hz),
7.68 (2H, brs) ESI-MS: 372 (M + H)

Production Example 10 (1) In the same manner as in Production Example 1- (7), 4-bromo-
2 from 1-butene and diethyl acetamidomalonate
-Diethyl acetamido-2- (3-butenyl) malonate was obtained. NMR (CDCl ₃ , δ): 1.27 (6H, t, J = 7Hz), 1.91
(2H, m), 2.03 (3H, s), 2.45 (2H, m), 4.25 (4H, q, J = 7H
z), 4.9-5.1 (2H, m), 5.75 (1H, m), 6.78 (1H, s)

(2) In the same manner as in Production Example 40- (4), 2-acetamido-2- [4- (dimethyloctyl) was prepared from diethyl 2-acetamido-2- (3-butenyl) malonate and dimethyloctylsilane. Diethyl (silyl) butyl] malonate was obtained. NMR (CDCl ₃ , δ): -0.09 (6H, s), 0.44 (4H,
m), 0.89 (2H, t, J = 7Hz), 1.05-1.4 (22H, m), 2.02 (3H,
s), 2.31 (2H, m), 4.24 (4H, q, J = 7Hz), 6.75 (1H, s)

Example 10 (1) In the same manner as in Example 1- (1), 2-acetamido-2- [4- (dimethyloctylsilyl) butyl]
From diethyl malonate to 2-acetamido-2- [4-
(Dimethyloctylsilyl) butyl] -1,3-propanediol was obtained. NMR (CDCl ₃ , δ): -0.07 (6H, s), 0.46 (4H,
m), 0.87 (3H, t, J = 7Hz), 1.2-1.35 (16H, m), 1.55-1.65
(2H, m), 2.03 (3H, s), 3.57 (2H, m), 3.82 (4H, m), 5.8
1 (1H, s)

(2) In the same manner as in Example 1- (2),
From 2-acetamido-2- [4- (dimethyloctylsilyl) butyl] -1,3-propanediol to 2-amino-2- [4- (dimethyloctylsilyl) butyl]-
1,3-propanediol hydrochloride was obtained. NMR (DMSO-d ₆ , δ): -0.07 (6H, s), 0.45
(4H, m), 0.84 (3H, t, J = 7Hz), 1.15-1.35 (16H, m), 1.50
(2H, m), 3.42 (4H, m), 5.29 (2H, t, J = 5Hz), 7.73 (3H, m
s)

Production Example 11 (1) In the same manner as in Production Example 40- (4), 2-acetamido-2-ethyl-2-acetamido-2- (2-propynyl) malonate and dimethyloctylsilane were used.
[2- (dimethyloctylsilyl) -2-propenyl]
Diethyl malonate was obtained. NMR (CDCl ₃ , δ): 0.02 (6H, s), 0.52 (2H,
m), 0.88 (3H, m), 1.25 (18H, m), 2.01 (3H, s), 3.18
(2H, s), 4.22 (4H, m), 5.45 (1H, m), 5.60 (1H, m), 6.75
(1H, s)

(2) In the same manner as in Production Example 1- (3),
Diethyl 2-acetamido-2- [2- (dimethyloctylsilyl) propyl] malonate was obtained from diethyl 2-acetamido-2- [2- (dimethyloctylsilyl) -2-propenyl] malonate. NMR (CDCl ₃ , δ): -0.80 (6H, s), 0.55 (2H,
m), 0.62 (1H, m), 0.93 (6H, m), 1.33 (18H, m), 2.10
(3H, d, J = 7Hz), 2.21 (1H, dd, J = 15,12Hz), 2.65 (1H, d, J
= 15Hz), 4.28 (4H, m)

Example 11 (1) In the same manner as in Example 1- (1), diethyl 2-acetamido-2- [2- (dimethyloctylsilyl) propyl] malonate was converted to diethyl 2-acetamido-2- [2
-(Dimethyloctylsilyl) propyl] -1,3-propanediol was obtained. NMR (CDCl ₃ , δ): 0.00 (6H, m), 0.53 (2H,
m), 0.78 (1H, m), 0.94 (3H, m), 1.08 (3H, d, J = 7Hz),
1.30 (13H, m), 1.78 (1H, d, J = 16Hz), 2.08 (3H, s), 3.63
(2H, m), 3.93 (2H, m), 5.73 (1H, br s)

(2) In the same manner as in Example 1- (2),
From 2-acetamido-2- [2- (dimethyloctylsilyl) propyl] -1,3-propanediol to 2-amino-2- [2- (dimethyloctylsilyl) propyl] -1,3-propanediol hydrochloride Obtained. NMR (CDCl ₃ , δ): -0.05 (3H, s), -0.02 (3H,
s), 0.52 (2H, m), 0.83 (1H, m), 0.91 (3H, m), 1.07 (3
(H, d, J = 7Hz), 1.30 (12H, m), 1.50 (1H, dd, J = 16,10Hz),
1.88 (1H, d, J = 16Hz), 3.90 (4H, m), 5.17 (1H, br s),
7.84 (3H, br s)

Production Example 12 (1) In the same manner as in Production Example 40- (4), diethyl 2- [3- (methyloctylphenylsilyl) propyl] malonate was prepared from diethyl 2-allylmalonate and methyloctylphenylsilane. Obtained. NMR (CDCl ₃ , δ): 0.23 (3H, s), 0.75 (4H,
m), 0.88 (3H, m), 1.22 (20H, m), 1.90 (2H, m), 3.32
(1H, t, J = 7Hz), 4.15 (4H, q, J = 7Hz), 7.33 (3H, m), 7.46
(2H, m)

(2) In the same manner as in Production Example 3- (6),
From 2- [3- (methyloctylphenylsilyl) propyl] malonate and O- (2,4-dinitrophenyl) hydroxylamine to 2-amino-2- [3
-(Methyloctylphenylsilyl) propyl] malonate was obtained. NMR (CDCl ₃ , δ): 0.22 (3H, s), 0.77 (4H,
m), 0.85 (3H, m), 1.20 (20H, m), 1.92 (2H, br), 1.98
(2H, m), 4.17 (4H, m), 7.33 (3H, m), 7.45 (2H, m)

Example 12 In the same manner as in Example 1- (1), 2-amino-2-
2-Amino-2- [3- (methyloctylphenylsilyl) propyl] -1,3-propanediol was obtained from diethyl [3- (methyloctylphenylsilyl) propyl] malonate. NMR (CDCl ₃ , δ): 0.23 (3H, s), 0.74 (2H,
m), 0.85 (2H, m), 1.25 (19H, m), 3.35-3.6 (4H, m), 4.
30 (4H, br), 7.35 (3H, m), 7.45 (2H, m)

Production Example 13 (1) In the same manner as in Production Example 40- (4), diethyl 2- [3- (hexylmethylphenylsilyl) propyl] malonate was prepared from diethyl 2-allylmalonate and hexylmethylphenylsilane. Obtained. NMR (CDCl ₃ , δ): 0.23 (3H, s), 0.75 (4H,
m), 0.85 (3H, m), 1.25 (14H, m), 1.90 (2H, m), 3.32
(1H, t, J = 7Hz), 4.17 (4H, q, J = 7Hz), 7.33 (3H, m), 7.45
(2H, m)

(2) In the same manner as in Production Example 3- (6),
From 2- [3- (hexylmethylphenylsilyl) propyl] malonate and O- (2,4-dinitrophenyl) hydroxylamine to 2-amino-2- [3
This gave diethyl-(hexylmethylphenylsilyl) propyl] malonate. NMR (CDCl ₃ , δ): 0.24 (3H, s), 1.77 (4H,
m), 1.86 (3H, m), 1.20 (16H, m), 1.85 (2H, br), 1.99
(2H, m), 4.18 (4H, m), 7.33 (3H, m), 7.45 (2H, m)

Example 13 In the same manner as in Example 1- (1), 2-amino-2-
2-Amino-2- [3- (hexylmethylphenylsilyl) propyl] -1,3-propanediol was obtained from diethyl [3- (hexylmethylphenylsilyl) propyl] malonate. NMR (CDCl ₃ , δ): 0.25 (3H, s), 0.74 (4H,
m), 0.85 (3H, m), 1.25 (12H, m), 1.90 (4H, br), 3.37
(2H, d, J = 12Hz), 3.49 (2H, d, J = 12Hz), 7.33 (3H, m), 7.
45 (2H, m)

Production Example 14 In the same manner as in Production Example 40- (4), 2-acetamido-2- [3- (butylmethylphenylsilyl) propyl was prepared from diethyl 2-acetamido-2-allylmalonate and butylmethylphenylsilane. ] Diethyl malonate was obtained. NMR (CDCl ₃ , δ): 0.73 (4H, m), 0.84 (3H, t,
J = 7Hz), 1.10 (2H, m), 1.20 (6H, m), 1.30 (4H, m), 1.9
9 (3H, s), 2.35 (2H, m), 4.20 (4H, q, J = 7Hz), 6.70 (1
H, s), 7.32 (3H, m), 7.45 (2H, m)

Example 14 (1) In the same manner as in Example 1- (1), diethyl 2-acetamido-2- [3- (butylmethylphenylsilyl) propyl] malonate was converted to 2-acetamido-2-malonate.
[3- (butylmethylphenylsilyl) propyl]-
1,3-propanediol was obtained. NMR (CDCl ₃ , δ): 0.25 (3H, s), 0.75 (4H,
m), 0.85 (3H, t, J = 7Hz), 1.28 (6H, m), 1.59 (2H, m),
1.97 (3H, s), 3.50 (2H, m), 3.70 (4H, m), 5.69 (1H,
s), 7.35 (3H, m), 7.48 (2H, m)

(2) In the same manner as in Example 1- (2),
2-acetamido-2- [3- (butylmethylphenylsilyl) propyl] -1,3-propanediol to 2
-Amino-2- [3- (butylmethylphenylsilyl)
[Propyl] -1,3-propanediol hydrochloride was obtained. NMR (CDCl ₃ , δ): 0.25 (3H, s), 0.75 (4H,
m), 0.85 (3H, t, J = 7Hz), 1.30 (6H, m), 1.65 (2H, m),
3.65 (4H, m), 5.90 (4H, br), 7.32 (3H, m), 7.45 (2H,
m)

Production Example 15 In the same manner as in Production Example 40- (4), 2-acetamido-2- [3- (dimethylphenylsilyl) propyl] malon was prepared from diethyl 2-acetamido-2-allylmalonate and dimethylphenylsilane. Diethyl acid was obtained. NMR (CDCl ₃ , δ): 0.22 (6H, s), 0.75 (2H, t,
J = 7Hz), 1.05-1.3 (8H, m), 1.99 (3H, s), 2.33 (2H, m),
4.19 (4H, q, J = 7Hz), 6.71 (1H, s), 7.33 (3H, m), 7.46
(2H, m)

Example 15 (1) In the same manner as in Example 1- (1), diethyl 2-acetamido-2- [3- (dimethylphenylsilyl) propyl] malonate was converted to diethyl 2-acetamido-2- [3
-(Dimethylphenylsilyl) propyl] -1,3-propanediol was obtained. NMR (CDCl ₃ , δ): 0.27 (6H, s), 1.73 (2H,
m), 1.26 (3H, t, J = 7Hz), 1.98 (3H, s), 3.51 (2H, m),
3.7-3.8 (4H, m), 5.70 (1H, s), 7.35 (3H, m), 7.49 (2H,
m)

(2) In the same manner as in Example 1- (2),
From 2-acetamido-2- [3- (dimethylphenylsilyl) propyl] -1,3-propanediol to 2-amino-2- [3- (dimethylphenylsilyl) propyl] -1,3-propanediol hydrochloride Obtained. NMR (DMSO-d ₆ , δ): 0.23 (6H, s), 0.67 (2
H, m), 1.32 (2H, m), 1.55 (2H, m), 3.40 (4H, m), 5.28
(2H, br s), 7.34 (3H, m), 7.50 (2H, m), 7.74 (3H, br
s)

Production Example 16 (1) In the same manner as in Production Example 1- (7), 6-bromo-
Diethyl 2-acetamido-2- (5-hexenyl) malonate was obtained from 1-hexene and diethyl acetamidomalonate. NMR (CDCl ₃ , δ): 1.12 (2H, m), 1.26 (6H, t,
J = 7Hz), 1.40 (2H, m), 2.03 (5H, m), 2.31 (2H, m), 4.2
4 (4H, q, J = 7Hz), 4.9-5.0 (2H, m), 5.75 (1H, m), 6.77
(1H, s)

(2) In the same manner as in Production Example 40- (4), 2-acetamido-2- [6- (dimethylphenyl) was prepared from diethyl 2-acetamido-2- (5-hexenyl) malonate and dimethylphenylsilane. Diethyl (silyl) hexyl] malonate was obtained. NMR (CDCl ₃ , δ): 0.23 (6H, s), 0.70 (2H,
m), 1.06 (2H, m), 1.2-1.3 (12H, m), 2.02 (3H, s), 2.29
(2H, m), 4.23 (4H, q, J = 7Hz), 6.74 (1H, s), 7.35 (3H,
m), 7.49 (2H, m)

Example 16 (1) In the same manner as in Example 1- (1), diethyl 2-acetamido-2- [6- (dimethylphenylsilyl) hexyl] malonate was converted to diethyl 2-acetamido-2- [6
-(Dimethylphenylsilyl) hexyl] -1,3-propanediol was obtained. NMR (CDCl ₃ , δ): 0.25 (6H, s), 0.72 (2H,
m), 1.15-1.35 (8H, m), 1.56 (2H, m), 2.03 (3H, s), 3.
56 (2H, m), 3.79 (4H, m), 5.79 (1H, s), 7.34 (3H, m),
7.49 (2H, m)

(2) In the same manner as in Example 1- (2),
From 2-acetamido-2- [6- (dimethylphenylsilyl) hexyl] -1,3-propanediol to 2-amino-2- [6- (dimethylphenylsilyl) hexyl] -1,3-propanediol hydrochloride Obtained. NMR (DMSO-d ₆ , δ): 0.23 (6H, s), 0.72 (2
(H, t, J = 7Hz), 1.15-1.35 (8H, m), 1.48 (2H, m), 3.43 (4
H, m), 5.30 (2H, t, J = 5Hz), 7.37 (3H, m), 7.50 (2H, m),
7.74 (3H, s)

Production Example 17 (1) In the same manner as in Production Example 1- (7), 8-bromo-
Diethyl 2-acetamido-2- (7-octenyl) malonate was obtained from 1-octene and diethyl acetamidomalonate. NMR (CDCl ₃ , δ): 1.09 (2H, m), 1.2-1.4 (10
H, m), 1.95-2.05 (5H, m), 2.30 (2H, m), 4.24 (4H, q, J =
7Hz), 4.9-5.05 (2H, m), 5.79 (1H, m), 6.76 (1H, s)

(2) In the same manner as in Preparation Example 40- (4), diethyl 2-acetamido-2- (7-octenyl) malonate and dimethylphenylsilane were used to give 2-acetamido-2- [8- (dimethylphenyl) silane. Diethyl (silyl) octyl] malonate was obtained. NMR (CDCl ₃ , δ): 0.23 (6H, s), 0.72 (2H, t,
J = 7Hz), 1.07 (2H, m), 1.15-1.35 (16H, m), 2.02 (3H,
s), 2.29 (2H, m), 4.23 (4H, q, J = 7Hz), 6.75 (1H, s),
7.33 (3H, m), 7.49 (2H, m)

Example 17 (1) In the same manner as in Example 1- (1), diethyl 2-acetamido-2- [8- (dimethylphenylsilyl) octyl] malonate was converted to diethyl 2-acetamido-2- [8
-(Dimethylphenylsilyl) octyl] -1,3-propanediol was obtained. NMR (CDCl ₃ , δ): 0.24 (6H, s), 0.72 (2H,
m), 1.2-1.35 (12H, m), 1.58 (2H, m), 2.03 (3H, s), 3.
57 (2H, m), 3.75-3.9 (4H, m), 5.82 (1H, s), 7.35 (3H,
m), 7.50 (2H, m)

(2) In the same manner as in Example 1- (2),
From 2-acetamido-2- [8- (dimethylphenylsilyl) octyl] -1,3-propanediol to 2-amino-2- [8- (dimethylphenylsilyl) octyl] -1,3-propanediol hydrochloride Obtained. NMR (DMSO-d ₆ , δ): 0.22 (6H, s), 0.70 (2
H, m), 1.15-1.3 (12H, m), 1.48 (2H, m), 3.42 (4H, m),
5.29 (2H, t, J = 5Hz), 7.36 (3H, m), 7.48 (2H, m), 7.72 (3
H, s)

Production Example 18 (1) In the same manner as in Production Example 3- (4), 9-decene-
10-Bromo-1-decene was obtained from 1-ol. NMR (CDCl ₃ , δ): 1.2-1.5 (10H, m), 1.84 (2
H, m), 2.03 (2H, m), 3.40 (2H, t, J = 7Hz), 4.9-5.05 (2
H, m), 5.81 (1H, m)

(2) In the same manner as in Production Example 3- (5),
Diethyl 2- (9-decenyl) malonate was obtained from 10-bromo-1-decene and diethyl malonate. NMR (CDCl ₃ , δ): 1.2-1.45 (18H, m), 1.88
(2H, m), 2.04 (2H, m), 3.30 (1H, t, J = 7Hz), 4.19 (4H, m
q, J = 7Hz), 4.9-5.05 (2H, m), 5.80 (1H, m)

(3) In the same manner as in Production Example 40- (4), diethyl 2- [10- (dimethylphenylsilyl) decyl] malonate was converted from diethyl 2- (9-decenyl) malonate and dimethylphenylsilane. Obtained. NMR (CDCl ₃ , δ): 0.24 (6H, s), 0.72 (2H, t,
J = 7Hz), 1.2-1.35 (22H, m), 1.88 (2H, q, J = 7Hz), 3.30
(1H, t, J = 7Hz), 4.19 (4H, q, J = 7Hz), 7.35 (3H, m), 7.50
(2H, m)

(4) In the same manner as in Production Example 3- (6),
Diethyl 2- [10- (dimethylphenylsilyl) decyl] malonate and O- (2,4-dinitrophenyl)
Diethyl 2-amino-2- [10- (dimethylphenylsilyl) decyl] malonate was obtained from hydroxylamine. NMR (CDCl ₃ , δ): 0.24 (6H, s), 0.72 (2H,
m), 1.15-1.35 (22H, m), 1.85-2.0 (4H, m), 4.21 (4H,
q, J = 7Hz), 7.33 (3H, m), 7.50 (2H, m)

Example 18 In the same manner as in Example 1- (2), 2-amino-2-
2-Amino-2- [10- (dimethylphenylsilyl) decyl] -1,3-propanediol hydrochloride was obtained from diethyl [10- (dimethylphenylsilyl) decyl] malonate. NMR (DMSO-d ₆ , δ): 0.23 (6H, s), 0.71 (2
(H, t, J = 7Hz), 1.15-1.35 (16H, m), 1.49 (2H, m), 3.44 (4
H, m), 5.30 (2H, t, J = 5Hz), 7.37 (3H, m), 7.50 (2H, m),
7.74 (3H, s)

Production Example 19 (1) In the same manner as in Production Example 1- (1), (10-undecenyloxy) tetrahydropyran was prepared from 10-undecen-1-ol and 3,4-dihydro-2H-pyran. I got NMR (CDCl ₃ , δ): 1.2-1.9 (20H, m), 2.03 (2
H, m), 3.38 (1H, m), 3.50 (1H, m), 3.72 (1H, m), 3.88
(1H, m), 4.58 (1H, m), 4.9-5.05 (2H, m), 5.81 (1H, m)

(2) In the same manner as in Preparation Example 40- (4), 2- [11- (dimethylphenylsilyl) undecyloxy] tetrahydropyran was prepared from (10-undecenyloxy) tetrahydropyran and dimethylphenylsilane. I got NMR (CDCl ₃ , δ): 0.24 (6H, s), 0.72 (2H,
m), 1.15-1.9 (24H, m), 3.38 (1H, m), 3.50 (1H, m), 3.
72 (1H, m), 3.87 (1H, m), 4.58 (1H, m), 7.34 (3H, m),
7.50 (2H, m)

(3) In the same manner as in Production Example 1- (4),
11- (Dimethylphenylsilyl) -1-undecanol was obtained from 2- [11- (dimethylphenylsilyl) undecyloxy] tetrahydropyran. NMR (CDCl ₃ , δ): 0.24 (6H, s), 0.72 (2H,
m), 1.15-1.4 (16H, m), 1.57 (2H, m), 3.62 (2H, t, J = 7H
z), 7.33 (3H, m), 7.50 (2H, m)

(4) A solution of 11- (dimethylphenylsilyl) -1-undecanol (2.84 g) in diethyl ether (20 ml) -acetonitrile (10 ml) was treated at 0 ° C. with imidazole (946 mg) and triphenylphosphine (3 .16 g). Mixture at 0 ° C
For 1 hour, iodine (3.29 g) was added to the mixture, and the mixture was stirred at 0 ° C. for 1 hour. Silica gel was added to the reaction mixture and filtered. The filtrate was concentrated and purified on a silica gel column [5% ethyl acetate (in hexane)].
-Iodo-11- (dimethylphenylsilyl) undecane (3.38 g) was obtained as a colorless oil. NMR (CDCl ₃ , δ): 0.24 (6H, s), 0.72 (2H,
m), 1.2-1.45 (16H, m), 1.80 (2H, m), 3.18 (2H, t, J = 7H
z), 7.34 (3H, m), 7.50 (2H, m)

(5) In the same manner as in Production Example 1- (7),
Diethyl 2-acetamido-2- [11- (dimethylphenylsilyl) undecyl] malonate was obtained from 1-iodo-11- (dimethylphenylsilyl) undecane and diethylacetamidomalonate. NMR (CDCl ₃ , δ): 0.25 (6H, s), 0.72 (2H,
m), 1.09 (2H, m), 1.2-1.35 (22H, m), 2.02 (3H, s), 2.
30 (2H, m), 4.24 (4H, q, J = 7Hz), 6.76 (1H, s), 7.33 (3
H, m), 7.50 (2H, m)

Example 19 (1) In the same manner as in Example 1- (1), diethyl 2-acetamido-2- [11- (dimethylphenylsilyl) undecyl] malonate was converted to diethyl 2-acetamido-2-.
[11- (dimethylphenylsilyl) undecyl]-
1,3-propanediol was obtained. NMR (CDCl ₃ , δ): 0.25 (6H, s), 0.77 (2H,
m), 1.2-1.45 (18H, m), 1.58 (2H, m), 2.04 (3H, s), 3.
57 (2H, m), 3.80 (4H, m), 5.80 (1H, s), 7.33 (3H, m),
7.50 (2H, m)

(2) In the same manner as in Example 1- (2),
From 2-acetamido-2- [11- (dimethylphenylsilyl) undecyl] -1,3-propanediol to 2
-Amino-2- [11- (dimethylphenylsilyl) undecyl] -1,3-propanediol hydrochloride was obtained. NMR (DMSO-d ₆ , δ): 0.22 (6H, s), 0.70 (2
H, m), 1.15-1.3 (18H, m), 1.48 (2H, m), 3.42 (4H, m),
5.29 (2H, t, J = 5Hz), 7.35 (3H, m), 7.48 (2H, m), 7.71
(3H, s)

Production Example 20 (1) In the same manner as in Production Example 3- (2), (4-chlorophenyl) dimethylsilane was obtained from dimethylsilylmagnesium chloride and 4-bromochlorobenzene. NMR (CDCl ₃ , δ): 0.32 (6H, d, J = 3 Hz), 4.41
(1H, m), 7.32 (2H, d, J = 8Hz), 7.46 (2H, d, J = 8Hz)

(2) In the same manner as in Production Example 40- (4), diethyl 2- (9-decenyl) malonate and (4
-Chlorophenyl) dimethylsilane to 2- [10-
Diethyl [(4-chlorophenyl) dimethylsilyl] decyl] malonate was obtained. NMR (CDCl ₃ , δ): 0.23 (6H, s), 0.65-0.76
(2H, m), 1.16-1.37 (16H, m), 1.25 (6H, t, J = 7Hz), 1.82
-1.93 (2H, m), 3.30 (1H, t, J = 7Hz), 4.18 (4H, q, J = 7H
z), 7.31 (2H, d, J = 8 Hz), 7.42 (2H, d, J = 8 Hz) ESI-MS: 491 (M + Na), 468 (MH)

(3) In the same manner as in Production Example 3- (6),
From 2- [10-[(4-chlorophenyl) dimethylsilyl] decyl] malonate and O- (2,4-dinitrophenyl) hydroxylamine to 2-amino-
Diethyl 2- [10-[(4-chlorophenyl) dimethylsilyl] decyl] malonate was obtained. NMR (CDCl ₃ , δ): 0.24 (6H, s), 0.66-0.75
(2H, m), 1.14-1.34 (16H, m), 1.26 (6H, t, J = 7Hz), 1.87
-2.00 (4H, m), 4.21 (4H, q, J = 7Hz), 7.32 (2H, d, J = 8H
z), 7.42 (2H, d, J = 8Hz) ESI-MS: 484 (M + H)

Example 20 In the same manner as in Example 1- (1), 2-amino-2-
[10-[(4-Chlorophenyl) dimethylsilyl] decyl] malonate is converted to 2-amino-2- [10-
[(4-Chlorophenyl) dimethylsilyl] decyl]-
1,3-propanediol hydrochloride was obtained. NMR (DMSO-d ₆ , δ): -0.25 (6H, s), 0.67-
0.78 (2H, m), 1.13-1.36 (16H, m), 1.43-1.57 (2H, m),
3.37-3.91 (4H, m), 5.29 (1H, t, J = 5Hz), 7.43 (2H, d, J =
8Hz), 7.53 (2H, d, J = 8Hz), 7.67 (2H, brs) ESI-MS: 400 (M + H)

Production Example 21 (1) Dimethyl (p-tolyl) silane was obtained from chlorodimethylsilane and p-tolylmagnesium bromide in the same manner as in Production Example 3- (2). NMR (CDCl ₃ , δ): 0.32 (6H, d, J = 3 Hz), 2.35
(3H, s), 4.41 (1H, m), 7.18 (2H, d, J = 8Hz), 7.43 (2H,
d, J = 8Hz)

(2) In the same manner as in Production Example 40- (4), 2- [10- [dimethyl (p-tolyl) is converted from diethyl 2- (9-decenyl) malonate and dimethyl (p-tolyl) silane. Diethyl [silyl] decyl] malonate was obtained. NMR (CDCl ₃ , δ): 0.23 (6H, s), 0.66-0.76
(2H, m), 1.16-1.36 (16H, m), 1.26 (6H, t, J = 7Hz), 1.82
-1.93 (2H, m), 2.34 (3H, s), 3.11 (1H, t, J = 7Hz), 4.18
(4H, q, J = 7Hz), 7.16 (2H, d, J = 8Hz), 7.40 (2H, d, J = 8Hz) ESI-MS: 471 (M + Na), 448 (MH)

(3) In the same manner as in Production Example 3- (6),
From 2- [10- [dimethyl (p-tolyl) silyl] decyl] malonate and O- (2,4-dinitrophenyl) hydroxylamine to 2-amino-2- [1
Diethyl 0- [dimethyl (p-tolyl) silyl] decyl] malonate was obtained. NMR (CDCl ₃ , δ): 0.23 (6H, s), 0.66-0.76
(2H, m), 1.16-1.34 (16H, m), 1.26 (6H, t, J = 7Hz), 1.86
-2.00 (2H, m), 2.34 (3H, s), 4.21 (4H, q, J = 7Hz), 7.17
(2H, d, J = 8Hz), 7.40 (2H, d, J = 8Hz) ESI-MS: 464 (M + H)

Example 21 In the same manner as in Example 1- (1), 2-amino-2-
2-Amino-2- [10- [dimethyl (p-tolyl) silyl] decyl] -1,3-propanediol hydrochloride was obtained from diethyl [10- [dimethyl (p-tolyl) silyl] decyl] malonate. . NMR (DMSO-d ₆ , δ): 0.22 (6H, s), 0.65-0.
74 (2H, m), 1.14-1.33 (16H, m), 1.45-1.55 (2H, m), 2.
30 (3H, s), 3.38-3.40 (4H, m), 5.30 (2H, t, J = 5Hz), 7.
19 (2H, d, J = 8Hz), 7.39 (2H, d, J = 8Hz), 7.60 (2H, brs) ESI-MS: 380 (M + H)

Production Example 22 (1) In the same manner as in Production Example 1- (5), 9-decene
9- from 1-ol and methanesulfonyl chloride
Decenyl methanesulfonate was obtained. NMR (CDCl ₃ , δ): 1.25-1.45 (8H, m), 1.75
(2H, m), 2.05 (2H, m), 3.00 (3H, s), 4.22 (2H, t, J = 7H
z), 4.97 (2H, m), 5.80 (1H, m)

(2) In the same manner as in Production Example 3- (5),
Diethyl 2- (9-decenyl) malonate was obtained from 9-decenyl methanesulfonate and diethyl malonate. NMR (CDCl ₃ , δ): 1.30 (18H, m), 1.88 (2H,
m), 2.03 (2H, m), 3.03 (1H, t, J = 7Hz), 4.18 (4H, q, J = 7
Hz), 4.92 (1H, m), 4.98 (1H, m), 5.80 (1H, m)

(3) In the same manner as in Production Example 40- (4), 2- [10-diethyl 2- (9-decenyl) malonate and dimethyl (3-methoxyphenyl) silane were used.
[Dimethyl (3-methoxyphenyl) silyl] decyl]
Diethyl malonate was obtained. NMR (CDCl ₃ , δ): 0.23 (6H, s), 0.72 (2H,
m), 1.25 (22H, m), 1.89 (2H, m), 3.30 (1H, t, J = 7Hz),
3.81 (3H, s), 4.19 (4H, q, J = 7Hz), 6.88 (1H, dd, J = 8,3H
z), 7.03 (1H, d, J = 3Hz), 7.08 (1H, d, J = 8Hz), 7.30 (1
(H, d, J = 8Hz)

(4) In the same manner as in Production Example 3- (6),
From 2- [10- [dimethyl (3-methoxyphenyl) silyl] decyl] malonate and O- (2,4-dinitrophenyl) hydroxylamine to 2-amino-
Diethyl 2- [10- [dimethyl (3-methoxyphenyl) silyl] decyl] malonate was obtained. NMR (CDCl ₃ , δ): 0.23 (6H, s), 0.73 (2H,
m), 1.25 (22H, m), 1.95 (4H, m), 4.20 (4H, q), 6.90
(1H, dd, J = 8,3Hz), 7.03 (1H, d, J = 3Hz), 7.08 (1H, d, J = 8
Hz), 7.30 (1H, d, J = 8Hz)

Example 22 In the same manner as in Example 1- (1), 2-amino-2-
[10- [dimethyl (3-methoxyphenyl) silyl]
[Didecyl] malonate from 2-amino-2- [10
-[Dimethyl (3-methoxyphenyl) silyl] decyl] -1,3-propanediol hydrochloride was obtained. NMR (DMSO-d ₆ , δ): 0.21 (6H, s), 0.70 (2
H, m), 1.22 (16H, m), 1.47 (2H, m), 3.40 (4H, m), 3.75
(3H, s), 5.25 (2H, br), 6.93 (1H, dd, J = 8,3Hz), 7.00
(1H, d, J = 3Hz), 7.05 (1H, d, J = 8Hz), 7.30 (1H, dd, J = 8,8
Hz), 7.50 (3H, br)

Production Example 23 (1) 1-bromo-method was prepared in the same manner as in Production Example 3- (2).
Dimethyl (4-propylphenyl) silane was obtained from 4-propylbenzene and dimethylsilylmagnesium chloride. NMR (CDCl ₃ , δ): 0.35 (6H, d, J = 5 Hz), 0.94
(3H, t, J = 7.5Hz), 1.58-1.7 (2H, m), 2.58 (2H, t, J = 7H
z), 4.4 (1H, m), 7.2 (2H, d, J = 7Hz), 7.45 (2H, d, J = 7H
z)

(2) In the same manner as in Production Example 40- (4), diethyl 2-allylmalonate and dimethyl (4-
Diethyl 2- [3- [dimethyl (4-propylphenyl) silyl] propyl] malonate was obtained from propylphenyl) silane. NMR (CDCl ₃ , δ): 0.22 (6H, s), 0.7-0.8 (2
H, m), 0.95 (3H, t, J = 7.5Hz), 1.2 (6H, t, J = 7.5Hz), 1.3
-1.4 (2H, m), 1.58-1.7 (2H, m), 1.85-1.95 (2H, m), 2.
58 (2H, t, J = 7Hz), 3.32 (1H, d, J = 7.5Hz), 4.18 (4H, q, J
= 7.5Hz), 7.15 (2H, d, J = 7Hz), 7.4 (2H, d, J = 7Hz) ESI-MS: 401 (M + Na)

(3) In the same manner as in Production Example 3- (6),
Diethyl 2- [3- [dimethyl (4-propylphenyl) silyl] propyl] malonate and O- (2,4-
Diethyl 2-amino-2- [3- [dimethyl (4-propylphenyl) silyl] propyl] malonate was obtained from (dinitrophenyl) hydroxylamine. NMR (CDCl ₃ , δ): 0.22 (6H, s), 0.74 (2H,
m), 0.96 (3H, t, J = 7.5Hz), 1.22 (6H, t, J = 7.5Hz), 1.22-
1.36 (2H, m), 1.56-1.7 (2H, m), 1.9-2.0 (2H, m), 2.58
(2H, t, J = 7.5Hz), 4.2 (4H, q, J = 7.5Hz), 7.16 (2H, t, J = 7
Hz), 7.4 (2H, d, J = 7Hz) ESI-MS: 394 (M + H)

Example 23 In the same manner as in Example 1- (1), 2-amino-2-
[3- [dimethyl (4-propylphenyl) silyl] propyl] malonate is converted to 2-amino-2- [3-
[Dimethyl (4-propylphenyl) silyl] propyl] -1,3-propanediol was obtained. NMR (DMSO-d ₆ , δ): 0.2 (6H, s), 0.64 (2
H, m), 0.92 (3H, t, J = 7.5Hz), 1.15-1.36 (4H, m), 1.56
(2H, m), 2.52 (2H, t, J = 7Hz), 3.05-3.18 (4H, m), 4.32
(2H, br), 7.16 (2H, d, J = 7Hz), 7.38 (2H, d, J = 7Hz) ESI-MS: 310 (M + H)

Production Example 24 (1) 1-bromo-method was prepared in the same manner as in Production Example 3- (2).
Dimethyl (4-pentylphenyl) silane was obtained from 4-pentylbenzene and dimethylsilylmagnesium chloride. NMR (CDCl ₃ , δ): 0.34 (6H, d, J = 5 Hz), 0.90
(3H, t, J = 7Hz), 1.22-1.4 (4H, m), 1.52-1.68 (2H, m), 2.
58 (2H, t, J = 7Hz), 4.4 (1H, m), 7.16 (2H, d, J = 7Hz), 7.
45 (2H, d, J = 7Hz)

(2) In the same manner as in Production Example 40- (4), diethyl 2-allylmalonate and dimethyl (4-
From 2-pentylphenyl) silane, diethyl 2- [3- [dimethyl (4-pentylphenyl) silyl] propyl] malonate was obtained. NMR (CDCl ₃ , δ): 0.22 (6H, s), 0.7-0.8 (2
H, m), 0.95 (3H, t, J = 7.5Hz), 1.2 (6H, t, J = 7.5Hz), 1.3
-1.4 (6H, m), 1.58-1.7 (2H, m), 1.85-1.95 (2H, m), 2.
58 (2H, t, J = 7Hz), 3.32 (1H, d, J = 7.5Hz), 4.18 (4H, q, J
= 7.5Hz), 7.15 (2H, d, J = 7Hz), 7.4 (2H, d, J = 7Hz) ESI-MS: 429 (M + Na)

(3) In the same manner as in Production Example 3- (6),
Diethyl 2- [3- [dimethyl (4-pentylphenyl) silyl] propyl] malonate and O- (2,4-
Diethyl 2-amino-2- [3- [dimethyl (4-pentylphenyl) silyl] propyl] malonate was obtained from dinitrophenyl) hydroxylamine. NMR (CDCl ₃ , δ): 0.22 (6H, s), 0.74 (2H,
m), 0.9 (3H, t, J = 7.5Hz), 1.22 (6H, t, J = 7.5Hz), 1.22-
1.36 (6H, m), 1.56-1.65 (2H, m), 1.88-2.0 (4H, m), 2.
56 (2H, t, J = 7.5Hz), 4.18 (4H, q, J = 7.5Hz), 7.16 (2H,
t, J = 7Hz), 7.38 (2H, d, J = 7Hz)

Example 24 In the same manner as in Example 1- (1), 2-amino-2-
[3- [dimethyl (4-pentylphenyl) silyl] propyl] malonate is converted to 2-amino-2- [3-
[Dimethyl (4-pentylphenyl) silyl] propyl] -1,3-propanediol was obtained. NMR (DMSO-d ₆ , δ): 0.2 (6H, s), 0.64 (2
H, m), 0.88 (3H, t, J = 7.5Hz), 1.1 (2H, br s), 1.2-1.6
(8H, m), 1.56 (2H, m), 2.52 (2H, t, J = 7Hz), 3.05-3.18
(4H, m), 4.32 (2H, br), 7.16 (2H, d, J = 7Hz), 7.38 (2H,
d, J = 7Hz) ESI-MS: 338 (M + H)

Production Example 25 (1) 1-bromo-method was prepared in the same manner as in Production Example 3- (2).
Dimethyl (4-heptylphenyl) silane was obtained from 4-heptylbenzene and dimethylsilylmagnesium chloride. NMR (CDCl ₃ , δ): 0.30 (6H, d, J = 5 Hz), 0.86
(3H, t, J = 7Hz), 1.2-1.36 (8H, m), 1.52-1.64 (2H, m), 2.
58 (2H, t, J = 7Hz), 4.4 (1H, m), 7.16 (2H, d, J = 7Hz), 7.
45 (2H, d, J = 7Hz)

(2) In the same manner as in Production Example 40- (4), diethyl 2-allylmalonate and dimethyl (4-
Diethyl 2- [3- [dimethyl (4-heptylphenyl) silyl] propyl] malonate was obtained from heptylphenyl) silane. NMR (CDCl ₃ , δ): 0.22 (6H, s), 0.7-0.8 (2
H, m), 0.95 (3H, t, J = 7.5Hz), 1.2 (6H, t, J = 7.5Hz), 1.2
-1.4 (10H, m), 1.58-1.7 (2H, m), 1.85-1.95 (2H, m),
2.58 (2H, t, J = 7Hz), 3.32 (1H, d, J = 7.5Hz), 4.18 (4H,
q, J = 7.5Hz), 7.15 (2H, d, J = 7Hz), 7.4 (2H, d, J = 7Hz) ESI-MS: 457 (M + Na)

(3) In the same manner as in Production Example 3- (6),
Diethyl 2- [3- [dimethyl (4-heptylphenyl) silyl] propyl] malonate and O- (2,4-
Diethyl 2-amino-2- [3- [dimethyl (4-heptylphenyl) silyl] propyl] malonate was obtained from dinitrophenyl) hydroxylamine. NMR (CDCl ₃ , δ): 0.22 (6H, s), 0.74 (2H,
m), 0.9 (3H, t, J = 7.5Hz), 1.22 (6H, t, J = 7.5Hz), 1.22-
1.36 (10H, m), 1.56-1.65 (2H, m), 1.88-2.0 (4H, m),
2.56 (2H, t, J = 7.5Hz), 4.18 (4H, q, J = 7.5Hz), 7.16 (2
H, t, J = 7Hz), 7.38 (2H, d, J = 7Hz) ESI-MS: 450 (M + H)

Example 25 In the same manner as in Example 1- (1), 2-amino-2-
[3- [dimethyl (4-heptylphenyl) silyl] propyl] malonate is converted to 2-amino-2- [3-
[Dimethyl (4-heptylphenyl) silyl] propyl] -1,3-propanediol was obtained. NMR (DMSO-d ₆ , δ): 0.2 (6H, s), 0.64 (2
H, m), 0.88 (3H, t, J = 7.5Hz), 1.1 (2H, br s), 1.2-1.6
(10H, m), 1.56 (2H, m), 2.52 (2H, t, J = 7Hz), 3.05-3.18
(4H, m), 4.32 (2H, br), 7.16 (2H, d, J = 7Hz), 7.38 (2
(H, d, J = 7Hz) ESI-MS: 366 (M + H)

Production Example 26 (1) To a suspension of magnesium (113 mg) in anhydrous tetrahydrofuran (5 ml) was added 2- [2- (4-bromophenyl) ethoxy] tetrahydropyran (1.20 g).
Of tetrahydrofuran (5 ml) was added, and the mixture was stirred at 70 ° C. for 2 hours. 6- (trimethylsilyl) hexyl methanesulfonate (956 mg) and 0.1 M dilithium tetrachlorocuprate in tetrahydrofuran (0.5 ml) in tetrahydrofuran (10
To the solution, the Grignard reagent prepared above was added to the solution under cooling with dry ice-methanol, and the mixture was added to -7 ml.
The mixture was stirred at 8 ° C for 0.5 hour and at room temperature for 18 hours. 1M Hydrochloric acid was added to the mixture, and the resulting mixture was extracted with ethyl acetate. The organic layer was washed successively with 1M hydrochloric acid, water and brine, dried over magnesium sulfate, and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane-ethyl acetate, 50: 1-20: 1) to give 2
-[2- [4- [6- (trimethylsilyl) hexyl]
Phenyl] ethoxy] tetrahydropyran (290 m
g) was obtained as a colorless oil. NMR (CDCl ₃ , δ): -0.04 (9H, s), 0.45 (2H, b
r), 1.21 (8H, br), 1.45-1.86 (6H, br), 2.56 (2H, t, J =
7Hz), 2.88 (2H, t, J = 7Hz), 3.45 (1H, m), 3.59 (1H, m),
3.76 (1H, m), 3.93 (1H, m), 4.58 (1H, m), 7.10-7.20
(4H, m)

(2) In the same manner as in Production Example 1- (4),
2- [2- [4- [6- (trimethylsilyl) hexyl] phenyl] ethoxy] tetrahydropyran to 2-
[4- [6- (Trimethylsilyl) hexyl] phenyl] ethanol was obtained. NMR (CDCl ₃ , δ): -0.03 (9H, s), 0.46 (2H,
m), 1.23-1.37 (6H, br), 1.56-1.66 (2H, br), 2.57 (2H,
t, J = 7Hz), 2.85 (2H, t, J = 7Hz), 3.85 (2H, br), 7.13 (4
H, s)

(3) In the same manner as in Production Example 19- (4), 2- [4- [6- (trimethylsilyl) hexyl]
[6- [4- (2-Iodoethyl) phenyl] hexyl] trimethylsilane was obtained from phenyl] ethanol. NMR (CDCl ₃ , δ): -0.03 (9H, s), 0.46 (2H, b
r), 1.23-1.38 (8H, br), 1.53-1.64 (2H, br), 2.58 (2H,
(t, J = 7Hz), 3.16 (2H, t, J = 7Hz), 3.33 (2H, t, J = 7Hz), 7.
11 (4H, m)

(4) In the same manner as in Production Example 3- (5),
[6- [4- (2-Iodoethyl) phenyl] hexyl] trimethylsilane and diethyl malonate
Diethyl [2- [4- [6- (trimethylsilyl) hexyl] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): -0.03 (9H, s), 0.46 (2H, b
r), 1.27 (6H, t, J = 7Hz), 1.27-1.35 (6H, br), 1.54-1.62
(2H, br), 2.21 (2H, m), 2.53-2.65 (4H, m), 3.35 (1H,
t, J = 7Hz), 4.19 (4H, q, J = 7Hz), 7.09 (4H, s)

(5) In the same manner as in Production Example 3- (6),
Diethyl 2- [2- [4- [6- (trimethylsilyl) hexyl] phenyl] ethyl] malonate and O-
Diethyl 2-amino-2- [2- [4- [6- (trimethylsilyl) hexyl] phenyl] ethyl] malonate was obtained from (2,4-dinitrophenyl) hydroxylamine. NMR (CDCl ₃ , δ): -0.04 (9H, s), 0.46 (2H, b
r), 1.28 (6H, t, J = 7Hz), 1.25-1.36 (6H, br), 1.57 (4H,
br), 2.25 (2H, m), 2.53-2.66 (4H, m), 4.21 (4H, q, J = 7
Hz), 7.10 (4H, s)

Example 26 (1) In the same manner as in Example 1- (1), 2-amino-
From diethyl 2- [2- [4- [6- (trimethylsilyl) hexyl] phenyl] ethyl] malonate to 2-amino-2- [2- [4- [6- (trimethylsilyl) hexyl] phenyl] ethyl] -1 , 3-propanediol was obtained. NMR (CDCl ₃ , δ): -0.03 (9H, s), 0.46 (2H, b
r), 1.20-1.35 (6H, br), 1.57 (2H, br), 1.68 (2H, m),
1.78 (4H, br), 2.53-2.65 (4H, m), 3.50 (2H, d, J = 10H
z), 3.61 (2H, d, J = 10Hz), 7.12 (4H, s)

(2) 2-amino-2- [2- [4- [6
-(Trimethylsilyl) hexyl] phenyl] ethyl]
-1,3-Propanediol (70.0 mg) was dissolved in methanol (1.5 ml), and methanol (0.9 ml) in which hydrogen chloride was dissolved was added to this solution. The solvent was distilled off and the residue was triturated with ethyl acetate to give 2-amino-
2- [2- [4- [6- (Trimethylsilyl) hexyl] phenyl] ethyl] -1,3-propanediol hydrochloride (70.6 mg) was obtained as an amorphous powder. NMR (CDCl ₃ , δ): -0.03 (9H, s), 0.47 (2H, b
r), 1.22-1.36 (6H, br), 1.56 (2H, br), 1.96 (2H, br),
2.40-2.70 (4H, br), 3.70-3.83 (4H, m), 7.10 (4H, m)

Production Example 27 (1) In the same manner as in Production Example 1- (2), 2- (3-propynyloxy) tetrahydropyran and chlorotrimethylsilane were used to prepare 2- (3-trimethylsilyl-2-propynyloxy) tetrahydropyran. I got Piran. NMR (CDCl ₃ , δ): 0.17 (9H, s), 1.45-1.9 (6
H, m), 3.52 (1H, m), 3.83 (1H, m), 4.25 (2H, m), 4.80
(1H, m)

(2) In the same manner as in Production Example 1- (3),
2- (3-trimethylsilyl-2-propynyloxy)
2- [3- (Trimethylsilyl) propoxy] tetrahydropyran was obtained from tetrahydropyran. NMR (CDCl ₃ , δ): -0.01 (9H, s), 0.48 (2H,
m), 1.45-1.95 (8H, m), 3.35 (1H, m), 3.49 (1H, m), 3.
68 (1H, m), 3.88 (1H, m), 4.58 (1H, m)

(3) In the same manner as in Production Example 1- (4),
3- (Trimethylsilyl) -1-propanol was obtained from 2- [3- (trimethylsilyl) propoxy] tetrahydropyran. NMR (DMSO-d ₆ , δ): -0.02 (9H, s), 0.43
(2H, m), 1.40 (2H, m), 3.34 (2H, m), 4.38 (1H, t, J = 6H
z)

(4) In the same manner as in Production Example 4- (2),
3- (trimethylsilyl) -1-propanol and p
-3- (Trimethylsilyl) propyl p-toluenesulfonate was obtained from -toluenesulfonyl chloride. NMR (CDCl ₃ , δ): -0.04 (9H, s), 0.44 (2H,
m), 1.62 (2H, m), 2.45 (3H, s), 3.98 (2H, t, J = 7Hz),
7.35 (2H, d, J = 8Hz), 7.81 (2H, d, J = 8Hz)

(5) 3- (trimethylsilyl) propyl p-toluenesulfonate (8.4 g), 2- (4-
Hydroxyphenyl) ethanol (8.1 g) and potassium carbonate (10.1 g) in 1,4-dioxane (70 g)
ml) was refluxed for 21 hours. The reaction mixture was poured into water, and the resulting mixture was extracted twice with ethyl acetate.
The combined organic solution was washed with brine, dried over magnesium sulfate and concentrated. The residue was purified on a silica gel column (hexane-ethyl acetate, 4: 1) to give 2- [4- [3-
(Trimethylsilyl) propoxy] phenyl] ethanol (6.80 g) was obtained as a colorless oil. NMR (CDCl ₃ , δ): 0.01 (9H, s), 0.60 (2H,
m), 1.38 (1H, t, J = 6Hz), 1.78 (2H, m), 2.80 (2H, t, J = 7
Hz), 3.8-3.95 (4H, m), 6.85 (2H, d, J = 8Hz), 7.13 (2H,
d, J = 8Hz)

(6) In the same manner as in Production Example 19- (4), 2- [4- [3- (trimethylsilyl) propoxy] phenyl] ethanol is converted to 2- [4- [3- (trimethylsilyl) propoxy] phenyl. Ethyl iodide was obtained. NMR (CDCl ₃ , δ): 0.01 (9H, s), 0.60 (2H,
m), 1.78 (2H, m), 3.10 (2H, t, J = 7Hz), 3.30 (2H, t, J = 7
Hz), 3.89 (27H, t), 6.83 (2H, d, J = 8Hz), 7.09 (2H, d, J
= 8Hz)

(7) In the same manner as in Production Example 1- (7),
From 2- [4- [3- (trimethylsilyl) propoxy] phenyl] ethyl iodide and diethyl acetamidomalonate, 2-acetamido-2- [2- [4- [3
This gave diethyl-(trimethylsilyl) propoxy] phenyl] ethyl] malonate. NMR (CDCl ₃ , δ): 0.01 (9H, s), 0.59 (2H,
m), 1.24 (6H, t, J = 7Hz), 1.77 (2H, m), 2.00 (3H, s),
2.42 (2H, m), 2.66 (2H, m), 3.88 (2H, t, J = 7Hz), 4.21
(4H, q, J = 7Hz), 6.75-6.85 (3H, m), 7.05 (2H, d, J = 8Hz)

Example 27 (1) In the same manner as in Example 1- (1), diethyl 2-acetamido-2- [2- [4- [3- (trimethylsilyl) propoxy] phenyl] ethyl] malonate was used. 2
-Acetamide-2- [2- [4- [3- (trimethylsilyl) propoxy] phenyl] ethyl] -1,3-propanediol was obtained. NMR (CDCl ₃ , δ): 0.01 (9H, s), 0.60 (2H,
m), 1.5-1.85 (4H, m), 2.01 (3H, s), 2.54 (2H, t, J = 7H
z), 3.55 (2H, m), 3.75-3.9 (6H, m), 5.81 (1H, s), 6.82
(2H, d, J = 8Hz), 7.08 (2H, d, J = 8Hz)

(2) In the same manner as in Example 1- (2),
2-acetamido-2- [2- [4- [3- (trimethylsilyl) propoxy] phenyl] ethyl] -1,3-
From propanediol, 2-amino-2- [2- [4-
[3- (Trimethylsilyl) propoxy] phenyl] ethyl] -1,3-propanediol hydrochloride was obtained. NMR (DMSO-d ₆ , δ): 0.00 (9H, s), 0.58 (2
H, m), 1.1-1.3 (4H, m), 2.53 (2H, m), 3.51 (4H, d, J = 5H
z), 3.87 (2H, t, J = 7Hz), 5.38 (2H, t, J = 5Hz), 6.82 (2
(H, d, J = 8Hz), 7.10 (2H, d, J = 8Hz), 7.86 (3H, br s)

Production Example 28 (1) 2- (4-Trimethylsilyl-3-butynyloxy) tetrahydropyran was prepared from 2- (3-butynyloxy) tetrahydropyran and chlorotrimethylsilane in the same manner as in Production Example 1- (2). Obtained. NMR (CDCl ₃ , δ): 0.14 (9H, s), 1.2-1.9 (20
H, m), 2.20 (2H, t, J = 7Hz), 3.37 (1H, m), 3.49 (1H, m),
3.72 (1H, m), 3.87 (1H, m), 4.58 (1H, m)

(2) In the same manner as in Production Example 1- (3),
From 2- (4-trimethylsilyl-3-butynyloxy) tetrahydropyran to 2- [4- (trimethylsilyl)
[Butoxy] tetrahydropyran. NMR (CDCl ₃ , δ): -0.02 (9H, s), 0.52 (2H,
m), 1.25-1.9 (10H, m), 3.39 (1H, m), 3.51 (1H, m), 3.
75 (1H, m), 3.88 (1H, m), 4.58 (1H, m)

(3) In the same manner as in Production Example 1- (4),
4- (Trimethylsilyl) -1-butanol was obtained from 2- [4- (trimethylsilyl) butoxy] tetrahydropyran. NMR (CDCl ₃ , δ): -0.01 (9H, s), 0.52 (2H,
m), 1.23 (1H, m), 1.38 (2H, m), 1.59 (2H, m), 3.66 (2
H, m)

(4) In the same manner as in Production Example 4- (2),
4- (trimethylsilyl) -1-butanol and p-
4- (Trimethylsilyl) butyl p-toluenesulfonate was obtained from toluenesulfonyl chloride. NMR (CDCl ₃ , δ): -0.07 (9H, s), 0.38 (2H,
m), 1.27 (2H, m), 1.64 (2H, m), 2.43 (3H, s), 4.02 (2
(H, t, J = 7Hz), 7.33 (2H, d, J = 8Hz), 7.78 (2H, d, J = 8Hz)

(5) In the same manner as in Production Example 27- (5), 4- [trimethylsilyl) butyl p-toluenesulfonate and 2- (4-hydroxyphenyl) ethanol were used to give 2- [4- [4- ( Trimethylsilyl) butoxy] phenyl] ethanol was obtained. NMR (CDCl ₃ , δ): 0.00 (9H, s), 0.55 (2H,
m), 1.35-1.55 (3H, m), 1.79 (2H, m), 2.81 (2H, t, J = 7H
z), 3.82 (2H, m), 3.94 (2H, t, J = 7Hz), 6.87 (2H, d, J = 8
Hz), 7.13 (2H, d, J = 8Hz)

(6) In the same manner as in Production Example 1- (5),
2- [4- [4- (Trimethylsilyl) butoxy] phenyl] ethanol and methanesulfonyl chloride gave 2- [4- [4- (trimethylsilyl) butoxy] phenyl] ethyl methanesulfonate. NMR (CDCl ₃ , δ): 0.00 (9H, s), 0.55 (2H,
m), 1.48 (2H, m), 1.80 (2H, m), 2.86 (3H, s), 2.99 (2
(H, t, J = 7Hz), 3.94 (2H, t, J = 7Hz), 4.38 (2H, t, J = 7Hz),
6.86 (2H, d, J = 8Hz), 7.13 (2H, d, J = 8Hz)

(7) In the same manner as in Production Example 1- (6),
2- [4- [4- (trimethylsilyl) butoxy] phenyl] ethyl methanesulfonate to 2- [4- [4
-(Trimethylsilyl) butoxy] phenyl] ethyl
I got iodide. NMR (CDCl ₃ , δ): 0.00 (9H, s), 0.55 (2H,
m), 1.48 (2H, m), 1.80 (2H, m), 3.11 (2H, t, J = 7Hz),
3.31 (2H, t, J = 7Hz), 3.94 (2H, t, J = 7Hz), 6.86 (2H, d, J
= 8Hz), 7.09 (2H, d, J = 8Hz)

(8) In the same manner as in Production Example 1- (7),
From 2- [4- [4- (trimethylsilyl) butoxy] phenyl] ethyl iodide and diethyl acetamidomalonate, 2-acetamido-2- [2- [4- [4-
Diethyl (trimethylsilyl) butoxy] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): -0.01 (9H, s), 0.54 (2H,
m), 1.25 (6H, m), 1.47 (2H, m), 1.79 (2H, m), 1.99 (3
H, s), 2.41 (2H, m), 2.65 (2H, m), 3.92 (2H, t, J = 7Hz),
4.20 (4H, m), 6.75-6.85 (3H, m), 7.05 (2H, d, J = 8Hz)

Example 28 (1) In the same manner as in Example 1- (1), diethyl 2-acetamido-2- [2- [4- [4- (trimethylsilyl) butoxy] phenyl] ethyl] malonate was used. 2-
Acetamide-2- [2- [4- [4- (trimethylsilyl) butoxy] phenyl] ethyl] -1,3-propanediol was obtained. NMR (CDCl ₃ , δ): -0.01 (9H, s), 0.54 (2H,
m), 1.47 (2H, m), 1.78 (2H, m), 1.9-2.0 (5H, m), 2.59
(2H, m), 3.61 (2H, d, J = 12Hz), 3.86 (2H, d, J = 12Hz),
3.92 (2H, t, J = 7Hz), 5.87 (1H, s), 6.82 (2H, d, J = 8Hz),
7.09 (2H, d, J = 8Hz)

(2) In the same manner as in Example 1- (2),
From 2-acetamido-2- [2- [4- [4- (trimethylsilyl) butoxy] phenyl] ethyl] -1,3-propanediol to 2-amino-2- [2- [4- [4
-(Trimethylsilyl) butoxy] phenyl] ethyl]
-1,3-propanediol hydrochloride was obtained. NMR (DMSO-d ₆ , δ): 0.00 (9H, s), 0.55 (2
H, m), 1.43 (2H, m), 1.65-1.8 (4H, m), 2.5-2.6 (2H,
m), 3.53 (4H, m), 3.93 (2H, t, J = 7Hz), 5.40 (2H, t, J = 5
Hz), 6.85 (2H, d, J = 8Hz), 7.11 (2H, d, J = 8Hz), 7.88 (3
H, s)

Production Example 29 (1) In the same manner as in Production Example 1- (1), 2- (4-pentynyloxy) tetrahydrofuran was prepared from 4-pentyn-1-ol and 3,4-dihydro-2H-pyran. I got Piran. NMR (CDCl ₃ , δ): 1.45-1.95 (9H, m), 2.31
(2H, m), 3.50 (2H, m), 3.85 (2H, m), 4.60 (1H, m)

(2) In the same manner as in Production Example 1- (2),
2- (5-Trimethylsilyl-4-pentynyloxy) tetrahydropyran was obtained from 2- (4-pentynyloxy) tetrahydropyran and chlorotrimethylsilane. NMR (CDCl ₃ , δ): 0.13 (9H, s), 1.45-1.9 (8
H, m), 2.34 (2H, t, J = 7Hz), 3.49 (2H, m), 3.85 (2H, m),
4.60 (1H, m)

(3) In the same manner as in Production Example 1- (3),
2- (5-trimethylsilyl-4-pentynyloxy)
2- [5- (Trimethylsilyl) pentyloxy] tetrahydropyran was obtained from tetrahydropyran. NMR (CDCl ₃ , δ): -0.02 (9H, s), 0.50 (2H,
m), 1.25-1.9 (12H, m), 3.38 (1H, m), 3.51 (1H, m), 3.
75 (1H, m), 3.88 (1H, m), 4.58 (1H, m)

(4) In the same manner as in Production Example 1- (4),
5- (Trimethylsilyl) -1-pentanol was obtained from 2- [5- (trimethylsilyl) pentyloxy] tetrahydropyran. NMR (CDCl ₃ , δ): -0.02 (9H, s), 0.49 (2H,
m), 1.2-1.45 (4H, m), 1.58 (2H, m), 3.64 (2H, m)

(5) In the same manner as in Production Example 4- (2),
5- (trimethylsilyl) -1-pentanol and p
5- (Trimethylsilyl) pentyl p-toluenesulfonate was obtained from -toluenesulfonyl chloride. NMR (CDCl ₃ , δ): -0.05 (9H, s), 0.42 (2H,
m), 1.15-1.4 (4H, m), 1.65 (2H, m), 2.44 (3H, s), 4.0
2 (2H, t, J = 7Hz), 7.34 (2H, d, J = 8Hz), 7.78 (2H, d, J = 8H
z)

(6) In the same manner as in Production Example 27- (5), 5- [trimethylsilyl) pentyl p-toluenesulfonate and 2- (4-hydroxyphenyl) ethanol were used to give 2- [4- [5- ( Trimethylsilyl) pentyloxy] phenyl] ethanol was obtained. NMR (CDCl ₃ , δ): -0.02 (9H, s), 0.50 (2H,
m), 1.25-1.55 (4H, m), 1.76 (2H, m), 2.80 (2H, t, J = 7H
z), 3.81 (2H, m), 3.92 (2H, t, J = 7Hz), 6.86 (2H, d, J = 8
Hz), 7.13 (2H, d, J = 8Hz)

(7) In the same manner as in Production Example 19- (4), 2- [4- [5- (trimethylsilyl) pentyloxy] phenyl] ethanol was converted to 2- [4- [5- (trimethylsilyl) pentyloxy]. ] Phenyl] ethyl
I got iodide. NMR (CDCl ₃ , δ): -0.02 (9H, s), 0.50 (2H,
m), 1.3-1.55 (4H, m), 1.77 (2H, m), 3.10 (2H, t, J = 7H
z), 3.31 (2H, t, J = 7Hz), 3.93 (2H, t, J = 7Hz), 6.84 (2H,
d, J = 8Hz), 7.09 (2H, d, J = 8Hz)

(8) In the same manner as in Production Example 1- (7),
From 2- [4- [5- (trimethylsilyl) pentyloxy] phenyl] ethyl iodide and diethyl acetamidomalonate, 2-acetamido-2- [2- [4
Diethyl-[5- (trimethylsilyl) pentyloxy] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): -0.02 (9H, s), 0.50 (2H,
m), 1.25 (6H, t, J = 7Hz), 1.3-1.55 (4H, m), 1.76 (2H,
m), 1.99 (3H, s), 2.41 (2H, m), 2.66 (2H, m), 3.90 (2
(H, t, J = 7Hz), 4.20 (4H, q, J = 7Hz), 6.75-6.85 (3H, m),
7.04 (2H, d, J = 8Hz)

Example 29 (1) Diethyl 2-acetamido-2- [2- [4- [5- (trimethylsilyl) pentyloxy] phenyl] ethyl] malonate was prepared in the same manner as in Example 1- (1). To 2-acetamido-2- [2- [4- [5- (trimethylsilyl) pentyloxy] phenyl] ethyl]-
1,3-propanediol was obtained. NMR (CDCl ₃ , δ): -0.02 (9H, s), 0.51 (2H,
m), 1.3-1.5 (4H, m), 1.77 (2H, m), 1.9-2.0 (5H, m),
2.60 (2H, m), 3.61 (2H, m), 3.75-3.95 (6H, m), 5.86
(1H, s), 6.81 (2H, d, J = 8Hz), 7.10 (2H, d, J = 8Hz)

(2) In the same manner as in Example 1- (2),
2-acetamido-2- [2- [4- [5- (trimethylsilyl) pentyloxy] phenyl] ethyl] -1,
From 3-propanediol to 2-amino-2- [2- [4
-[5- (Trimethylsilyl) pentyloxy] phenyl] ethyl] -1,3-propanediol hydrochloride was obtained. NMR (DMSO-d ₆ , δ): -0.02 (9H, s), 0.50
(2H, m), 1.3-1.5 (4H, m), 1.55-1.7 (4H, m), 2.56 (2H, m
m), 3.52 (4H, m), 3.90 (2H, t, J = 7Hz), 5.39 (2H, t, J = 5
Hz), 6.84 (2H, d, J = 8Hz), 7.10 (2H, d, J = 8Hz), 7.88 (3
H, br s)

Production Example 30 (1) In the same manner as in Production Example 1- (2), 2- [3- [butynyloxy) tetrahydropyran and chlorodimethylethylsilane were used to give 2- [3- [4- (dimethylethylsilyl) [Butinyl] oxy] tetrahydropyran was obtained. NMR (CDCl ₃ , δ): 0.11 (6H, s), 0.57 (2H, q,
J = 7Hz), 0.98 (3H, t, J = 7Hz), 1.46-1.90 (6H, m), 2.53
(2H, t, J = 6Hz), 3.48-3.94 (4H, m), 4.67 (1H, t, J = 4Hz)

(2) In the same manner as in Production Example 1- (3),
2- [3- [4- (dimethylethylsilyl) butynyl]
2- [4- (Dimethylethylsilyl) butoxy] tetrahydropyran was obtained from [oxy] tetrahydropyran. NMR (CDCl ₃ , δ): -0.06 (6H, s), 0.42-0.55
(4H, m), 0.92 (3H, t, J = 7Hz), 1.30-1.91 (10H, m), 3.39
(1H, m), 3.50 (1H, m), 3.74 (1H, m), 3.87 (1H, m), 4.
58 (1H, t, J = 4Hz)

(3) In the same manner as in Production Example 1- (4),
From 2- [4- (dimethylethylsilyl) butoxy] tetrahydropyran to 4- (dimethylethylsilyl) -1-
Butanol was obtained. NMR (CDCl ₃ , δ): -0.06 (6H, s), 0.40-0.54
(4H, m), 0.92 (3H, t, J = 7Hz), 1.19 (1H, t, J = 6Hz), 1.36
(2H, m), 1.58 (2H, m), 3.62 (2H, q, J = 6Hz)

(4) 4- (dimethylethylsilyl) -1
-Butanol (2.0 g) in anhydrous dichloromethane (40
ml) solution with 2- [2- (4-hydroxyphenyl)
Ethyl diethyl diethylmalonate (3.5 g) and triphenylphosphine (3.6 g) were added. Under ice-cooling, diethyl azodicarboxylate (2.8 ml) was added dropwise to the mixture. The mixture was stirred for 1 hour under ice cooling, and the solvent was distilled off under reduced pressure. The residue was dissolved in chloroform (6.0 ml) and diluted with hexane (60 ml). The mixture was stirred at room temperature for 1 hour. The precipitate was filtered off and washed with hexane-ethyl acetate (4: 1). Collect the filtrate and washings,
The solvent was distilled off under reduced pressure to give a white slurry (11.
2 g) were obtained. The residue was purified by silica gel column chromatography (hexane-ethyl acetate, 49: 1-19: 1) to give diethyl 2- [2- [4- [4- [4- (dimethylethylsilyl) butoxy] phenyl] ethyl] malonate ( 2.16 g) was obtained as a colorless oil. NMR (CDCl ₃ , δ): -0.05 (6H, s), 0.42-0.58
(4H, m), 0.92 (3H, t, J = 7Hz), 1.25 (6H, t, J = 6Hz), 1.45
(2H, m), 1.77 (2H, m), 2.16 (2H, q, J = 6Hz), 2.58 (2H, m
(t, J = 6Hz), 3.33 (1H, t, J = 6Hz), 3.93 (2H, t, J = 6Hz), 4.
18 (4H, q, J = 6Hz), 6.81 (2H, d, J = 8Hz), 7.07 (2H, d, J = 8H
z)

(5) In the same manner as in Production Example 3- (6),
Diethyl 2- [2- [4- [4- (dimethylethylsilyl) butoxy] phenyl] ethyl] malonate and O-
Diethyl 2-amino-2- [2- [4- [4- (dimethylethylsilyl) butoxy] phenyl] ethyl] malonate was obtained from (2,4-dinitrophenyl) hydroxylamine. NMR (CDCl ₃ , δ): -0.05 (6H, s), 0.42-0.59
(4H, m), 0.91 (3H, t, J = 7.5Hz), 1.27 (6H, t, J = 7.5Hz),
1.39-1.52 (2H, m), 1.72-1.85 (2H, m), 2.06-2.27 (2H, m
m), 2.54-2.63 (2H, m), 3.92 (2H, t, J = 7.5Hz), 4.21 (4
H, q, J = 7.5Hz), 6.81 (2H, d, J = 7.5Hz), 7.09 (2H, d, J = 7.
(5Hz)

Example 30 (1) In the same manner as in Example 1- (1), 2-amino-
From 2- [2- [4- [4- (dimethylethylsilyl) butoxy] phenyl] ethyl] malonate to 2-amino-2- [2- [4- [4- (dimethylethylsilyl) butoxy] phenyl] [Ethyl] -1,3-propanediol was obtained. Melting point: 122-123 ° C NMR (CDCl ₃ , δ): -0.05 (6H, s), 0.43-0.60
(4H, m), 0.92 (3H, t, J = 7.5Hz), 1.40-1.53 (2H, m), 1.6
4-1.86 (4H, m), 2.55-2.64 (2H, m), 3.50 (2H, d, J = 10H
z), 3.62 (2H, d, J = 10Hz), 3.94 (2H, t, J = 7.5Hz), 6.83
(2H, d, J = 7.5Hz), 7.11 (2H, d, J = 7.5Hz)

(2) In the same manner as in Example 26- (2), 2-amino-2- [2- [4- [4- (dimethylethylsilyl) butoxy] phenyl] ethyl] -1,3-
From propanediol, 2-amino-2- [2- [4-
[4- (dimethylethylsilyl) butoxy] phenyl]
[Ethyl] -1,3-propanediol hydrochloride was obtained. Melting point: 113-115 ° C NMR (CDCl ₃ , δ): -0.04 (6H, s), 0.43-0.59
(4H, m), 0.92 (3H, t, J = 7.5Hz), 1.36-1.50 (2H, m), 1.6
9-1.80 (2H, m), 1.90-2.01 (2H, m), 2.52-2.62 (2H, m),
3.75-3.88 (6H, m), 6.73 (2H, d, J = 7.5Hz), 7.09 (2H, m
d, J = 7.5Hz)

Production Example 31 (1) In the same manner as in Production Example 1- (2), 2- [3- [4- (dimethylpropylsilyl) tetrahydropyran and 2- (3-butynyloxy) tetrahydropyran were used. [Butinyl] oxy] tetrahydropyran was obtained. NMR (CDCl ₃ , δ): 0.12 (6H, s), 0.60 (2H,
m), 0.97 (3H, t, J = 7Hz), 1.28-1.90 (8H, m), 2.53 (2H,
(t, J = 7Hz), 3.48-3.60 (2H, m), 3.79-3.93 (2H, m), 4.66
(1H, m)

(2) In the same manner as in Production Example 1- (3),
2- [4- (Dimethylpropylsilyl) butoxy] tetrahydropyran was obtained from 2- [3- [4- (dimethylpropylsilyl) butynyl] oxy] tetrahydropyran. NMR (CDCl ₃ , δ): -0.04 (6H, s), 0.45-0.55
(4H, m), 0.94 (3H, t, J = 7Hz), 1.24-1.42 (4H, m), 1.48-
1.90 (8H, m), 3.34-3.42 (1H, m), 3.46-3.55 (1H, m),
3.69-3.78 (1H, m), 3.82-3.91 (1H, m), 4.58 (1H, m)

(3) In the same manner as in Production Example 1- (4),
From 2- [4- (dimethylpropylsilyl) butoxy] tetrahydropyran to 4- (dimethylpropylsilyl)-
1-butanol was obtained. NMR (CDCl ₃ , δ): -0.03 (6H, s), 0.47-0.56
(4H, m), 0.95 (3H, t, J = 7Hz), 1.20-1.42 (5H, m), 1.53-
1.64 (2H, m), 3.64 (2H, br)

(4) In the same manner as in Production Example 4- (2),
4- (Dimethylpropylsilyl) butyl p-toluenesulfonate was obtained from 4- (dimethylpropylsilyl) -1-butanol and p-toluenesulfonyl chloride. NMR (CDCl ₃ , δ): -0.03, 0.03 (6H, s), 0.34
-0.52 (4H, m), 0.93 (3H, t, J = 7Hz), 1.22-1.34 (4H, m),
1.59-1.68 (2H, m), 2.45 (3H, s), 4.03 (2H, t, J = 7Hz),
7.33 (2H, d, J = 8Hz), 7.79 (2H, d, J = 8Hz)

(5) In the same manner as in Production Example 27- (5), diethyl 2- [2- (4-hydroxyphenyl) ethyl] malonate and 4- (dimethylpropylsilyl)
From butyl p-toluenesulfonate to 2- [2- [4-
Diethyl [4- (dimethylpropylsilyl) butoxy] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): 0.06, 0.08 (6H, s), 0.56-
0.66 (4H, m), 1.03 (3H, t, J = 7Hz), 1.37 (6H, t, J = 7Hz),
1.38-1.46 (2H, m), 1.50-1.60 (2H, m), 1.88 (2H, m),
2.27 (2H, q, J = 7Hz), 2.69 (2H, t, J = 7Hz), 3.42 (1H, t, J
= 7Hz), 4.03 (2H, t, J = 7Hz), 4.29 (4H, q, J = 7Hz), 6.90
(2H, d, J = 8Hz), 7.18 (2H, d, J = 8Hz)

(6) In the same manner as in Production Example 3- (6),
Diethyl 2- [2- [4- [4- (dimethylpropylsilyl) butoxy] phenyl] ethyl] malonate and O
Diethyl 2-amino-2- [2- [4- [4- (dimethylpropylsilyl) butoxy] phenyl] ethyl] malonate was obtained from-(2,4-dinitrophenyl) hydroxylamine. NMR (CDCl ₃ , δ): -0.04 (6H, s), 0.46-0.57
(4H, m), 0.95 (3H, t, J = 7Hz), 1.28 (6H, t, J = 7Hz), 1.29
-1.52 (6H, m), 1.73-1.82 (2H, m), 2.19-2.25 (2H, m),
2.54-2.62 (2H, m), 3.93 (2H, t, J = 7Hz), 4.23 (4H, q, J =
7Hz), 6.82 (2H, d, J = 8Hz), 7.09 (2H, d, J = 8Hz)

Example 31 (1) In the same manner as in Example 1- (1), 2-amino-
From diethyl 2- [2- [4- [4- (dimethylpropylsilyl) butoxy] phenyl] ethyl] malonate to 2-
Amino-2- [2- [4- [4- (dimethylpropylsilyl) butoxy] phenyl] ethyl] -1,3-propanediol was obtained. NMR (CDCl ₃ , δ): -0.04 (6H, s), 0.48-0.58
(4H, m), 0.97 (3H, t, J = 7Hz), 1.28-1.38 (2H, m), 1.40-
1.52 (2H, m), 1.65-1.72 (2H, m), 1.74-1.85 (2H, m),
1.95 (4H, br), 2.59 (2H, m), 3.51 (2H, d, J = 10Hz), 3.6
2 (2H, d, J = 10Hz), 3.93 (2H, t, J = 7Hz), 6.83 (2H, d, J = 8H
z), 7.10 (2H, d, J = 8Hz)

(2) In the same manner as in Example 26- (2), 2-amino-2- [2- [4- [4- (dimethylpropylsilyl) butoxy] phenyl] ethyl] -1,3
-Propanediol to 2-amino-2- [2- [4-
[4- (Dimethylpropylsilyl) butoxy] phenyl] ethyl] -1,3-propanediol hydrochloride was obtained. NMR (DMSO-d ₆ , δ): -0.05 (6H, s), 0.45-
0.55 (4H, m), 0.93 (3H, t, J = 7Hz), 1.25-1.47 (4H, m),
1.66-1.78 (4H, m), 3.50 (4H, br), 3.91 (2H, t, J = 7Hz),
5.35 (2H, br), 6.82 (2H, d, J = 8Hz), 7.09 (2H, d, J = 8H
z)

Production Example 32 (1) Sodium hydride (60% in oil) anhydrous N, N-
4-pentyn-1-ol (26 ml) was added dropwise to a suspension of dimethylformamide (117 ml) under ice cooling,
The mixture was stirred for 1 hour under ice cooling. Benzyl bromide (3
9.9 ml) was added to the mixture and stirred at room temperature overnight.
The reaction mixture was poured into ice water (1.0 liter) and extracted twice with ether. The organic layer was collected, washed sequentially with water and brine, dried over magnesium sulfate, and evaporated under reduced pressure. The residue was purified by vacuum distillation to give 5-benzyloxy-1-pentyne (47.1 g) as a colorless oil. NMR (CDCl ₃ , δ): 1.83 (2H, m), 1.94 (1H, t,
J = 3Hz), 2.33 (2H, td, J = 7,3Hz), 3.58 (2H, d, J = 7Hz),
4.52 (2H, s), 7.24-7.40 (5H, m)

(2) In the same manner as in Production Example 1- (2),
5-Benzyloxy-1- (dimethylethylsilyl) -1-pentyne was obtained from 5-benzyloxy-1-pentyne and chlorodimethylethylsilane. NMR (CDCl ₃ , δ): 0.10 (6H, s), 0.56 (2H, q,
J = 7Hz), 0.97 (3H, t, J = 7Hz), 1.83 (2H, m), 2.35 (2H,
(t, J = 7Hz), 3.58 (2H, t, J = 7Hz), 4.52 (2H, s), 7.22-7.4
0 (5H, m)

(3) In the same manner as in Production Example 1- (3),
5-benzyloxy-1- (dimethylethylsilyl)-
1-pentyne to 5- (dimethylethylsilyl) -1-
Butanol was obtained. NMR (CDCl ₃ , δ): -0.06 (6H, s), 0.42-0.54
(4H, m), 0.92 (3H, t, J = 7Hz), 1.18-1.63 (7H, m), 3.64
(2H, t, J = 6Hz)

(4) In the same manner as in Production Example 30- (4), 2- (dimethylethylsilyl) -1-butanol and diethyl 2- [2- (4-hydroxyphenyl) ethyl] malonate were used to give 2- Diethyl [2- [4- [5- (dimethylethylsilyl) pentyloxy] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): -0.05 (6H, s), 0.43-0.57
(4H, m), 0.93 (3H, t, J = 7.5Hz), 1.29 (6H, t, J = 7.5Hz),
1.32-1.54 (4H, m), 1.72-1.84 (2H, m), 2.04-2.25 (2H,
m), 2.60 (2H, br t, J = 7.5Hz), 3.34 (1H, t, J = 7.5Hz),
3.93 (2H, t, J = 7.5Hz), 4.21 (4H, q, J = 7.5Hz), 6.82 (2
(H, d, J = 7.5Hz), 7.09 (2H, d, J = 7.5Hz)

(5) In the same manner as in Production Example 3- (6),
From 2- [2- [4- [5- (dimethylethylsilyl) pentyloxy] phenyl] ethyl] malonate and O- (2,4-dinitrophenyl) hydroxylamine to 2-amino-2- [2- [ Diethyl 4- [5- (dimethylethylsilyl) pentyloxy] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): -0.05 (6H, s), 0.41-0.57
(4H, m), 0.92 (3H, t, J = 7.5Hz), 1.28 (6H, t, J = 7.5Hz),
1.31-1.56 (4H, m), 1.71-1.83 (2H, m), 2.05 (2H, br
s), 2.19-2.29 (2H, m), 2.55-2.65 (2H, m), 3.93 (2H,
t, J = 7.5Hz), 4.23 (4H, q, J = 7.5Hz), 6.82 (2H, d, J = 7.5H
z), 7.10 (2H, d, J = 7.5Hz)

Example 32 (1) In the same manner as in Example 1- (1), 2-amino-
From 2- [2- [4- [5- (dimethylethylsilyl) pentyloxy] phenyl] ethyl] malonate to 2-amino-2- [2- [4- [5- (dimethylethylsilyl) pentyloxy] [Phenyl] ethyl] -1,3
-Propanediol was obtained. _{Mp: 124~127 ℃ NMR (CDCl 3 -CD} 3 OD, δ): - 0.05 (6H,
s), 0.42-0.57 (4H, m), 0.92 (3H, t, J = 7.5Hz), 1.29-1.
53 (4H, m), 1.60-1.82 (4H, m), 2.52-2.63 (2H, m), 3.49
(2H, br d, J = 10Hz), 3.60 (2H, br d, J = 10Hz), 3.92 (2
H, t, J = 7.5Hz), 6.82 (2H, d, J = 7.5Hz), 7.10 (2H, d, J = 7.5
Hz)

(2) In the same manner as in Example 26- (2), 2-amino-2- [2- [4- [5- (dimethylethylsilyl) pentyloxy] phenyl] ethyl]-
From 1,3-propanediol, 2-amino-2- [2-
[4- [5- (Dimethylethylsilyl) pentyloxy] phenyl] ethyl] -1,3-propanediol hydrochloride was obtained. Melting point: 113-116 ° C NMR (CDCl ₃ -CD ₃ OD, δ): -0.05 (6H,
s), 0.43-0.56 (4H, m), 0.92 (3H, t, J = 7.5Hz), 1.28-1.
53 (4H, m), 1.68-1.83 (2H, m), 1.91-2.03 (2H, m), 2.55
-2.68 (2H, m), 3.74 (2H, d, J = 10Hz), 3.83 (2H, br d, J =
10Hz), 3.89 (2H, t, J = 7.5Hz), 6.79 (2H, d, J = 7.5Hz),
7.12 (2H, d, J = 7.5Hz)

Production Example 33 (1) By the same method as in Production Example 1- (2), 5-benzyloxy-1- (dimethylpropylsilyl) -1 was prepared from 5-benzyloxy-1-pentyne and chlorodimethylpropylsilane. -Pentin was obtained. NMR (CDCl ₃ , δ): 0.19 (6H, s), 0.57 (2H,
m), 0.97 (3H, t, J = 7Hz), 1.32-1.48 (2H, m), 1.78-1.88
(2H, m), 2.36 (2H, t, J = 7Hz), 3.56 (2H, t, J = 7Hz), 4.50
(2H, s), 7.31 (5H, m)

(2) In the same manner as in Production Example 1- (3),
5-benzyloxy-1- (dimethylpropylsilyl)
-1-pentyne to 5- (dimethylpropylsilyl)-
1-pentanol was obtained. NMR (CDCl ₃ , δ): -0.06 (6H, s), 0.40-0.53
(4H, m), 0.94 (3H, t, J = 7Hz), 1.20-1.43 (6H, br), 1.50
-1.63 (3H, m), 3.62 (2H, t, J = 7Hz)

(3) In the same manner as in Production Example 19- (4), 2- (4-benzyloxyphenyl) ethyl iodide was obtained from 2- (4-benzyloxyphenyl) ethanol. NMR (CDCl ₃ , δ): -0.03 (9H, s), 0.47 (2H, b
r), 1.24-1.37 (8H, br), 1.54-1.64 (2H, br), 2.58 (2H, br
(t, J = 7Hz), 3.14 (2H, t, J = 7Hz), 3.34 (2H, t, J = 7Hz), 7.
10 (4H, m)

(4) In the same manner as in Production Example 3- (5),
Diethyl 2- [2- (4-benzyloxyphenyl) ethyl] malonate was obtained from diethyl malonate and 2- (4-benzyloxyphenyl) ethyl iodide. NMR (CDCl ₃ , δ): 1.27 (6H, t, J = 7Hz), 2.19
(2H, m), 2.60 (2H, t, J = 7Hz), 3.32 (1H, t, J = 7Hz), 4.18
(4H, q, J = 7Hz), 5.04 (2H, s), 6.91 (2H, d, J = 8Hz), 7.1
0 (2H, d, J = 8Hz), 7.30-7.44 (5H, m)

(5) In the same manner as in Production Example 1- (3),
Diethyl 2- [2- (4-hydroxyphenyl) ethyl] malonate was obtained from diethyl 2- [2- (4-benzyloxyphenyl) ethyl] malonate. NMR (CDCl ₃ , δ): 1.28 (6H, t, J = 7Hz), 2.27
(2H, m), 2.60 (2H, t, J = 7Hz), 3.33 (1H, t, J = 7Hz), 4.20
(4H, q, J = 7Hz), 4.89 (1H, br), 6.75 (2H, d, J = 8Hz), 7.
02 (2H, d, J = 8Hz)

(6) In the same manner as in Production Example 30- (4), 2- (dimethylpropylsilyl) -5-pentanol and diethyl 2- [2- (4-hydroxyphenyl) ethyl] malonate were used to give 2 Diethyl-[2- [4- [5- (dimethylpropylsilyl) pentyloxy] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): -0.05 (6H, s), 0.43-0.55
(4H, m), 0.94 (3H, t, J = 7Hz), 1.28 (6H, t, J = 7Hz), 1.28
-1.50 (6H, m), 1.70-1.82 (2H, m), 2.12-2.22 (2H, m),
2.59 (2H, t, J = 7Hz), 3.33 (1H, t, J = 7Hz), 3.91 (2H, t, J
= 7Hz), 4.18 (4H, q, J = 7Hz), 6.81 (2H, d, J = 8Hz), 7.07
(2H, d, J = 8Hz)

(7) In the same manner as in Production Example 3- (6),
From 2- [2- [4- [5- (dimethylpropylsilyl) pentyloxy] phenyl] ethyl] malonate and O- (2,4-dinitrophenyl) hydroxylamine to 2-amino-2- [2- [ Diethyl 4- [5- (dimethylpropylsilyl) pentyloxy] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): -0.05 (6H, s), 0.43-0.54
(4H, m), 0.95 (3H, t, J = 7Hz), 1.28 (6H, t, J = 7Hz), 1.29
-1.50 (6H, m), 1.70-1.82 (2H, m), 2.19-2.28 (2H, m),
2.54-2.63 (2H, m), 3.93 (2H, t, J = 7Hz), 4.21 (4H, q, J =
7Hz), 6.80 (2H, d, J = 8Hz), 7.08 (2H, d, J = 8Hz)

Example 33 (1) In the same manner as in Example 1- (1), 2-amino-
From 2- [2- [4- [5- (dimethylpropylsilyl) pentyloxy] phenyl] ethyl] malonate to 2-amino-2- [2- [4- [5- (dimethylpropylsilyl) pentyloxy] [Phenyl] ethyl]-
1,3-propanediol was obtained. NMR (CDCl ₃ , δ): -0.04 (6H, s), 0.46-0.53
(4H, m), 0.95 (3H, t, J = 7Hz), 1.25-1.50 (6H, m), 1.60-
1.82 (8H, m), 2.56-2.62 (2H, m), 3.49 (2H, d, J = 10Hz),
3.60 (2H, d, J = 10Hz), 3.91 (2H, t, J = 7Hz), 6.81 (2H,
d, J = 8Hz), 7.08 (2H, d, J = 8Hz)

(2) In the same manner as in Example 26- (2), 2-amino-2- [2- [4- [5- (dimethylpropylsilyl) pentyloxy] phenyl] ethyl]-
From 1,3-propanediol, 2-amino-2- [2-
[4- [5- (Dimethylpropylsilyl) pentyloxy] phenyl] ethyl] -1,3-propanediol hydrochloride was obtained. NMR (DMSO-d ₆ , δ): -0.05 (6H, s), 0.44-
0.53 (4H, m), 0.93 (3H, t, J = 7Hz), 1.24-1.48 (6H, m),
1.64-1.78 (4H, m), 2.55 (2H, br), 3.50 (4H, br), 3.90
(2H, t, J = 7Hz), 5.38 (2H, br), 6.83 (2H, d, J = 8Hz), 7.0
8 (2H, d, J = 8Hz)

Production Example 34 (1) In the same manner as in Production Example 32- (1), 4-benzyloxy-1-butyne was obtained from benzyl bromide and 3-butyn-1-ol. NMR (CDCl ₃ , δ): 2.00 (1H, d, J = 2 Hz), 2.51
(2H, m), 3.51 (2H, d, J = 7.5Hz), 4.57 (2H, s), 7.25-7.3
8 (5H, m)

(2) In the same manner as in Production Example 1- (2),
1- (Dimethylisopropylsilyl) -4-benzyloxy-1-butyne was obtained from 4-benzyloxy-1-butyne and chlorodimethylisopropylsilane. NMR (CDCl ₃ , δ): 0.09 (6H, s), 1.00 (6H, d,
J = 7.5Hz), 2.56 (2H, t, J = 7.5Hz), 3.61 (2H, t, J = 7.5H
z), 4.56 (2H, s), 7.28-7.38 (5H, m)

(3) In the same manner as in Production Example 1- (3),
4- (Dimethylisopropylsilyl) -1-butanol was obtained from 1- (dimethylisopropylsilyl) -4-benzyloxy-1-butyne. NMR (CDCl ₃ , δ): -0.06 (6H, s), 0.54 (2H,
m), 0.76 (1H, m), 0.96 (6H, d, J = 7.5Hz), 1.3-1.44 (2
H, m), 1.54-1.66 (2H, m), 3.66 (2H, t, J = 7Hz)

(4) 1- (Dimethylisopropylsilyl) -4-benzyloxy-1-butyne and 2- [2- (4-hydroxyphenyl) ethyl] malone in the same manner as in Production Example 30- (4). 2- [2-
Diethyl [4- [4- (dimethylisopropylsilyl) butoxy] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): -0.06 (6H, s), 0.5-0.6 (2
H, m), 0.7-0.8 (1H, m), 0.94 (6H, d, J = 7.5Hz), 1.28 (6
(H, t, J = 7.5Hz), 1.4-1.54 (2H, m), 1.74-1.84 (2H, m),
2.12-2.24 (2H, m), 2.54-2.64 (2H, m), 3.34 (1H, t, J =
7.5Hz), 3.94 (2H, t, J = 7.5Hz), 4.2 (4H, q, J = 7.5Hz),
6.82 (2H, d, J = 8Hz), 7.1 (2H, d, J = 8Hz)

(5) In the same manner as in Production Example 3- (6),
From 2- [2- [4- [4- (dimethylisopropylsilyl) butoxy] phenyl] ethyl] malonate and O- (2,4-dinitrophenyl) hydroxylamine to 2-amino-2- [2- [4 -[4- (dimethylisopropylsilyl) butoxy] phenyl] ethyl]
Diethyl malonate was obtained. NMR (CDCl ₃ , δ): 0.06 (6H, s), 0.56-0.64
(2H, m), 0.82 (1H, m), 1.0 (6H, d, J = 7Hz), 1.34 (6H, t,
J = 7Hz), 1.45-1.9 (6H, m), 2.25-2.34 (2H, m), 2.6-2.7
(2H, m), 4.0 (2H, t, J = 7Hz), 4.28 (4H, q, J = 7Hz), 6.88
(2H, d, J = 7Hz), 7.16 (2H, d)

Example 34 In the same manner as in Example 1- (1), 2-amino-2-
From diethyl [2- [4- [4- (dimethylisopropylsilyl) butoxy] phenyl] ethyl] malonate to 2-
Amino-2- [2- [4- [4- (dimethylisopropylsilyl) butoxy] phenyl] ethyl] -1,3-propanediol was obtained. _{Mp: 112.5~120 ℃ NMR (CDCl 3,} δ): - 0.06 (6H, s), 0.5-0.6 (2
H, m), 0.8 (1H, m), 0.9 (6H, t, J = 7Hz), 1.4-1.5 (2H, m),
1.6-1.7 (2H, m), 2.5-2.6 (2H, m), 3.5 (4H, ABx), 3.9
(2H, t, J = 7.5Hz), 6.75 (2H, d, J = 8Hz), 7.1 (2H, d, J = 8H)
z)

Production Example 35 (1) In the same manner as in Production Example 1- (2), 2- [3- (dimethylpropylsilyl) -2 was prepared from 2- (2-propynyloxy) tetrahydropyran and chlorodimethylpropylsilane. -Propynyloxy] tetrahydropyran was obtained. NMR (CDCl ₃ , δ): 0.14 (6H, s), 0.62 (2H,
m), 0.98 (2H, t, J = 7Hz), 1.3-1.9 (8H, m), 3.52 (1H,
m), 3.84 (1H, m), 4.27 (2H, m), 4.82 (1H, m)

(2) In the same manner as in Production Example 1- (3),
2- [3- (Dimethylpropylsilyl) propoxy] tetrahydropyran was obtained from 2- [3- (dimethylpropylsilyl) -2-propynyloxy] tetrahydropyran. NMR (CDCl ₃ , δ): -0.03 (6H, s), 0.49 (4H,
m), 0.95 (3H, t, J = 7Hz), 1.34 (2H, m), 1.45-1.9 (8H,
m), 3.36 (1H, m), 3.50 (1H, m), 3.68 (1H, m), 3.89 (1
H, m), 4.58 (1H, m)

(3) In the same manner as in Production Example 1- (4),
From 2- [3- (dimethylpropylsilyl) propoxy] tetrahydropyran to 3- (dimethylpropylsilyl)
-1-propanol was obtained. NMR (CDCl ₃ , δ): -0.03 (6H, s), 0.48 (4H,
m), 0.98 (3H, t, J = 7Hz), 1.31 (2H, m), 1.54 (2H, m), 3.
59 (2H, m)

(4) In the same manner as in Production Example 1- (7),
Diethyl 2-acetamido-2- [2- (4-benzyloxyphenyl) ethyl] malonate was obtained from 2- (4-benzyloxyphenyl) ethyl iodide and diethyl acetamidomalonate. NMR (CDCl ₃ , δ): 1.23 (6H, t, J = 7 Hz), 1.98
(3H, s), 2.42 (2H, m), 2.66 (2H, m), 4.19 (4H, m), 5.0
2 (2H, s), 6.75 (1H, s), 6.88 (2H, d, J = 8Hz), 7.05 (2
(H, d, J = 8Hz), 7.25-7.45 (5H, m)

(5) In the same manner as in Production Example 1- (3),
Diethyl 2-acetamido-2- [2- (4-hydroxyphenyl) ethyl] malonate was obtained from diethyl 2-acetamido-2- [2- (4-benzyloxyphenyl) ethyl] malonate. _{NMR (DMSO-d 6, δ} ): 1.14 (6H, t, J = 7Hz),
1.93 (3H, s), 2.30 (4H, s), 4.11 (4H, q, J = 7Hz), 6.67
(2H, d, J = 8Hz), 6.90 (2H, d, J = 8Hz), 8.31 (1H, s), 9.17
(1H, s)

(6) In the same manner as in Production Example 30- (4), diethyl 2-acetamido-2- [2- (4-hydroxyphenyl) ethyl] malonate and 3- (dimethylpropylsilyl) -1- Diethyl 2-acetamido-2- [2- [4- [3- (dimethylpropylsilyl) propoxy] phenyl] ethyl] malonate was obtained from propanol. NMR (CDCl ₃ , δ): -0.01 (6H, s), 0.5-0.65
(4H, m), 0.97 (2H, t, J = 7Hz), 1.2-1.4 (8H, m), 1.77 (2
H, m), 1.99 (3H, s), 2.42 (2H, m), 2.66 (2H, m), 3.88
(2H, t, J = 7Hz), 4.20 (4H, m), 6.75-6.82 (3H, m), 7.05
(2H, d, J = 8Hz)

Example 35 (1) In the same manner as in Example 1- (1), 2-acetamido-2- [2- [4- [3- (dimethylpropylsilyl) propoxy] phenyl] ethyl] malonic acid From diethyl to 2-acetamido-2- [2- [4- [3- (dimethylpropylsilyl) propoxy] phenyl] ethyl]
-1,3-propanediol was obtained. NMR (CDCl ₃ , δ): -0.01 (6H, s), 0.5-0.65
(4H, m), 0.97 (2H, t, J = 7Hz), 1.35 (2H, m), 1.77 (2H,
m), 1.9-2.0 (5H, m), 2.59 (2H, m), 3.61 (2H, m), 3.78
(2H, t, J = 7Hz), 3.87 (4H, m), 5.85 (1H, s), 6.82 (2H,
d, J = 8Hz), 7.10 (2H, d, J = 8Hz)

(2) In the same manner as in Example 1- (2),
2-acetamido-2- [2- [4- [3- (dimethylpropylsilyl) propoxy] phenyl] ethyl]-
From 1,3-propanediol, 2-amino-2- [2-
[4- [3- (dimethylpropylsilyl) propoxy]
[Phenyl] ethyl] -1,3-propanediol hydrochloride was obtained. NMR (DMSO-d ₆ , δ): -0.01 (6H, s), 0.5-0.
65 (4H, m), 0.94 (2H, t, J = 7Hz), 1.23 (2H, m), 1.65-1.
8 (4H, m), 2.56 (2H, m), 3.52 (4H, d, J = 5Hz), 3.88 (2
(H, t, J = 7Hz), 5.39 (2H, t, J = 5Hz), 6.84 (2H, d, J = 8Hz),
7.11 (2H, d, J = 8Hz), 7.84 (3H, br s)

Production Example 36 (1) In the same manner as in Production Example 27- (5), 3- (trimethylsilyl) propyl p-toluenesulfonate and 3- (4-hydroxyphenyl) -1-propanol were used to give 3- [ 4- [3- (Trimethylsilyl) propoxy] phenyl] -1-propanol was obtained. NMR (CDCl ₃ , δ): -0.02 (9H, s), 0.57 (2H,
m), 1.22 (1H, m), 1.7-1.9 (4H, m), 2.61 (2H, t, J = 7H
z), 3.65 (2H, m), 3.86 (2H, t, J = 7Hz), 6.79 (2H, d, J = 8
Hz), 7.08 (2H, d, J = 8Hz)

(2) In the same manner as in Production Example 19- (4), 3- [4- [3- (trimethylsilyl) propoxy] phenyl] -1-propanol was converted to 3- [4- [3
-(Trimethylsilyl) propoxy] phenyl] propyl iodide was obtained. NMR (CDCl ₃ , δ): 0.00 (9H, s), 0.59 (2H,
m), 1.78 (2H, m), 2.09 (2H, m), 2.66 (2H, t, J = 7Hz),
3.16 (2H, t, J = 7Hz), 3.89 (2H, t, J = 7Hz), 6.81 (2H, d, J
= 8Hz), 7.09 (2H, d, J = 8Hz)

(3) In the same manner as in Production Example 1- (7),
From 3- [4- [3- (trimethylsilyl) propoxy] phenyl] propyl iodide and diethyl acetamidomalonate, 2-acetamido-2- [3- [4-
Diethyl [3- (trimethylsilyl) propoxy] phenyl] propyl] malonate was obtained. NMR (CDCl ₃ , δ): 0.01 (9H, s), 0.59 (2H,
m), 1.22 (6H, t, J = 7Hz), 1.39 (2H, m), 1.77 (2H, m),
2.02 (3H, s), 2.37 (2H, m), 2.54 (2H, t, J = 7Hz), 3.88
(2H, t, J = 7Hz), 4.21 (4H, q, J = 7Hz), 6.75-6.85 (3H, m),
7.02 (2H, d, J = 8Hz)

Example 36 (1) In the same manner as in Example 1- (1), diethyl 2-acetamido-2- [3- [4- [3- (trimethylsilyl) propoxy] phenyl] propyl] malonate was used. 2-acetamido-2- [3- [4- [3- (trimethylsilyl) propoxy] phenyl] propyl] -1,3
-Propanediol was obtained. NMR (CDCl ₃ , δ): 0.01 (9H, s), 0.59 (2H,
m), 1.5-1.85 (4H, m), 2.00 (3H, s), 2.54 (2H, t, J = 7H
z), 3.54 (2H, m), 3.7-3.9 (6H, m), 5.79 (1H, s), 6.81
(2H, d, J = 8Hz), 7.08 (2H, d, J = 8Hz)

(2) In the same manner as in Example 1- (2),
2-acetamido-2- [3- [4- [3- (trimethylsilyl) propoxy] phenyl] propyl] -1,3
-Propanediol to 2-amino-2- [3- [4-
[3- (Trimethylsilyl) propoxy] phenyl] propyl] -1,3-propanediol hydrochloride was obtained. NMR (DMSO-d ₆ , δ): 0.00 (9H, s), 0.58 (2
H, m), 1.5-1.75 (6H, m), 2.47 (2H, m), 3.42 (4H, m), 3.
87 (2H, t, J = 7Hz), 5.30 (2H, t, J = 5Hz), 6.81 (2H, d, J = 8
Hz), 7.08 (2H, d, J = 8Hz), 7.72 (3H, br s)

Production Example 37 (1) In the same manner as in Production Example 1- (2), 2- [4- (butyldimethylsilyl) -3-amine was prepared from 2- (3-butynyloxy) tetrahydropyran and butylchlorodimethylsilane. [Butynyloxy] tetrahydropyran was obtained. NMR (CDCl ₃ , δ): 0.12 (6H, s), 0.53-0.63
(2H, m), 0.89 (3H, t, J = 7Hz), 1.23-1.39 (6H, m), 1.47-
1.89 (4H, m), 2.53 (2H, t, J = 7Hz), 3.47-3.59 (2H, m),
3.77-3.94 (2H, m), 4.67 (1H, dd, J = 5,3Hz)

(2) In the same manner as in Production Example 1- (3),
2- [4- (Butyldimethylsilyl) butyloxy] tetrahydropyran was obtained from 2- [4- (butyldimethylsilyl) -3-butynyloxy] tetrahydropyran. NMR (CDCl ₃ , δ): -0.06 (6H, s), 0.42-0.54
(4H, m), 0.87 (3H, t, J = 7Hz), 1.17-1.42 (8H, m), 1.46-
1.89 (6H, m), 3.37 (1H, m), 3.50 (1H, m), 3.73 (1H, m),
3.87 (1H, m), 4.58 (1H, dd, J = 5,3Hz)

(3) In the same manner as in Production Example 1- (4),
From 2- [4- (butyldimethylsilyl) butyloxy] tetrahydropyran to 4- (butyldimethylsilyl)-
1-butanol was obtained. NMR (CDCl ₃ , δ): -0.05 (6H, s), 0.44-0.55
(4H, m), 0.88 (3H, t, J = 7Hz), 1.18-1.42 (6H, m), 1.53-
1.64 (3H, m), 3.61-3.69 (2H, m)

(4) In the same manner as in Preparation Example 30- (4), 2- (butyldimethylsilyl) -1-butanol and 2- [2- (4-hydroxyphenyl) ethyl] malonate were converted to 2- Diethyl [2- [4- [4- (butyldimethylsilyl) butoxy] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): -0.05 (6H, s), 0.45-0.6
(4H, m), 0.98 (3H, t, J = 7Hz), 1.27 (6H, t, J = 7Hz), 1.2-
1.4 (4H, m), 1.4-1.55 (2H, m), 1.75-1.85 (2H, m), 2.1
5-2.21 (2H, m), 2.6 (2H, t, J = 7Hz), 3.31 (1H, t, J = 7H
z), 3.94 (2H, t, J = 7Hz), 4.19 (4H, q, J = 7Hz), 6.83 (2
(H, d, J = 8Hz), 7.09 (2H, d, J = 8Hz)

(5) In the same manner as in Production Example 3- (6),
Diethyl 2- [2- [4- [4- (butyldimethylsilyl) butoxy] phenyl] ethyl] malonate and O-
Diethyl 2-amino-2- [2- [4- [4- (butyldimethylsilyl) butoxy] phenyl] ethyl] malonate was obtained from (2,4-dinitrophenyl) hydroxylamine. NMR (CDCl ₃ , δ): -0.05 (6H, s), 0.45-0.6
(4H, m), 0.98 (3H, t, J = 7Hz), 1.27 (6H, t, J = 7Hz), 1.2-
1.4 (4H, m), 1.4-1.55 (2H, m), 1.75-1.85 (2H, m), 2.0
(2H, br), 2.15-2.21 (2H, m), 2.6-2.5 (2H, m), 3.94
(2H, t, J = 7Hz), 4.19 (4H, q, J = 7Hz), 6.83 (2H, d, J = 8Hz),
7.09 (2H, d, J = 8Hz)

Example 37 In the same manner as in Example 1- (1), 2-amino-2-
[2- [4- [4- (butyldimethylsilyl) butoxy] phenyl] ethyl] malonate to 2-amino-2- [2- [4- [4- (butyldimethylsilyl)
[Butoxy] phenyl] ethyl] -1,3-propanediol was obtained. Melting point: 98-100 ° C NMR (CDCl ₃ , δ): -0.06 (6H, s), 0.5-0.6 (4
H, m), 0.9 (3H, t, J = 7Hz), 1.2-1.3 (4H, m), 1.4-1.5 (2
H, m), 1.6-1.7 (2H, m), 1.7-1.8 (2H, m), 2.5-2.6 (2H,
m), 3.5 (4H, ABx), 3.9 (2H, t, J = 7.5Hz), 6.75 (2H, d, J
= 8Hz), 7.1 (2H, d, J = 8Hz)

Production Example 38 (1) Pentamethylene dimethanesulfonate was obtained from 1,5-pentanediol and methanesulfonyl chloride in the same manner as in Production Example 1- (5). NMR (CDCl ₃ , δ): 1.58 (2H, m), 1.81 (4H,
m), 3.02 (6H, s), 4.26 (2H, t, J = 7Hz)

(2) In the same manner as in Production Example 3- (2),
6- (Trimethylsilyl) hexyl methanesulfonate was obtained from pentamethylene dimethanesulfonate and trimethylsilylmethylmagnesium chloride. NMR (CDCl ₃ , δ): -0.02 (9H, s), 0.48 (2H,
m), 1.2-1.5 (6H, m), 1.75 (2H, m), 3.00 (3H, s), 4.23
(2H, t, J = 7Hz)

(3) By a method similar to that of Production Example 27- (5), 6- (trimethylsilyl) hexylmethanesulfonate and diethyl 2-acetamido-2- [2- (4-hydroxyphenyl) ethyl] malonate were used. Diethyl 2-acetamido-2- [2- [4- [6- (trimethylsilyl) hexyloxy] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): -0.03 (9H, s), 0.49 (2H,
m), 1.2-1.5 (12H, m), 1.76 (2H, m), 1.99 (3H, s), 2.4
2 (2H, m), 2.66 (2H, m), 3.92 (2H, t, J = 7Hz), 4.21 (4
(H, q, J = 7Hz), 6.75-6.85 (3H, m), 7.05 (2H, d, J = 8Hz)

Example 38 (1) Diethyl 2-acetamido-2- [2- [4- [6- (trimethylsilyl) hexyloxy] phenyl] ethyl] malonate was prepared in the same manner as in Example 1- (1). To 2-acetamido-2- [2- [4- [6- (trimethylsilyl) hexyloxy] phenyl] ethyl]-
1,3-propanediol was obtained. NMR (CDCl ₃ , δ): -0.02 (9H, s), 0.49 (2H,
m), 1.25-1.5 (6H, m), 1.76 (2H, m), 1.9-2.0 (5H, m),
2.60 (2H, m), 3.62 (2H, m), 3.75-3.95 (6H, m), 5.85
(1H, s), 6.83 (2H, d, J = 8Hz), 7.10 (2H, d, J = 8Hz)

(2) In the same manner as in Example 1- (2),
2-acetamido-2- [2- [4- [6- (trimethylsilyl) hexyloxy] phenyl] ethyl] -1,
From 3-propanediol to 2-amino-2- [2- [4
-[6- (Trimethylsilyl) hexyloxy] phenyl] ethyl] -1,3-propanediol hydrochloride was obtained. NMR (DMSO-d ₆ , δ): -0.03 (9H, s), 0.48
(2H, m), 1.2-1.45 (6H, m), 1.6-1.8 (4H, m), 2.53 (2H,
m), 3.51 (4H, d, J = 5Hz), 3.90 (2H, t, J = 7Hz), 5.38 (2
(H, t, J = 5Hz), 6.84 (2H, d, J = 8Hz), 7.10 (2H, d, J = 8Hz),
7.90 (3H, br s)

Production Example 39 (1) In the same manner as in Production Example 1- (5), hexamethylene dimethanesulfonate was obtained from 1,6-hexanediol and methanesulfonyl chloride. NMR (CDCl ₃ , δ): 1.48 (4H, m), 1.78 (4H,
m), 3.01 (6H, s), 4.23 (4H, t, J = 7Hz)

(2) In the same manner as in Production Example 3- (2),
7- (Trimethylsilyl) heptyl methanesulfonate was obtained from hexamethylene dimethanesulfonate and trimethylsilylmethylmagnesium chloride. NMR (CDCl ₃ , δ): -0.02 (9H, s), 0.48 (2H,
m), 1.2-1.5 (8H, m), 1.76 (2H, m), 3.01 (3H, s), 4.22
(2H, t, J = 7Hz)

(3) In the same manner as in Production Example 1- (6),
7- (Trimethylsilyl) heptyl iodide was obtained from 7- (trimethylsilyl) heptylmethanesulfonate. NMR (CDCl ₃ , δ): -0.02 (9H, s), 0.47 (2H,
m), 1.2-1.5 (8H, m), 1.84 (2H, m), 3.19 (2H, t, J = 7Hz)

(4) In the same manner as in Production Example 27- (5), the compound was converted from 7- (trimethylsilyl) heptyliodide and diethyl 2-acetamido-2- [2- (4-hydroxyphenyl) ethyl] malonate by -Acetamide-
Diethyl 2- [2- [4- [7- (trimethylsilyl) heptyloxy] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): -0.02 (9H, s), 0.48 (2H,
m), 1.2-1.5 (14H, m), 1.77 (2H, m), 2.00 (3H, s), 2.4
3 (2H, m), 2.66 (2H, m), 3.92 (2H, t, J = 7Hz), 4.31 (4
(H, q, J = 7Hz), 6.76-6.84 (3H, m), 7.06 (2H, d, J = 8Hz)

Example 39 (1) Diethyl 2-acetamido-2- [2- [4- [7- (trimethylsilyl) heptyloxy] phenyl] ethyl] malonate was prepared in the same manner as in Example 1- (1). To 2-acetamido-2- [2- [4- [7- (trimethylsilyl) heptyloxy] phenyl] ethyl]-
1,3-propanediol was obtained. NMR (CDCl ₃ , δ): -0.03 (9H, s), 0.47 (2H,
m), 1.2-1.5 (8H, m), 1.76 (2H, m), 1.9-2.0 (5H, m),
2.59 (2H, m), 3.61 (2H, m), 3.72 (2H, t, J = 7Hz), 3.8-
3.95 (4H, m), 5.83 (1H, s), 6.82 (2H, d, J = 8Hz), 7.10
(2H, d, J = 8Hz)

(2) In the same manner as in Example 1- (2),
2-acetamido-2- [2- [4- [7- (trimethylsilyl) heptyloxy] phenyl] ethyl] -1,
From 3-propanediol to 2-amino-2- [2- [4
-[7- (Trimethylsilyl) heptyloxy] phenyl] ethyl] -1,3-propanediol hydrochloride was obtained. NMR (DMSO-d ₆ , δ): -0.03 (9H, s), 0.47
(2H, m), 1.2-1.5 (8H, m), 1.6-1.8 (4H, m), 2.53 (2H, m
m), 3.52 (4H, d, J = 5Hz), 3.91 (2H, t, J = 7Hz), 5.38 (2H,
t, J = 5Hz), 6.84 (2H, d, J = 8Hz), 7.10 (2H, d, J = 8Hz), 7.
85 (3H, br s)

Production Example 40 (1) In the same manner as in Production Example 27- (5), 2- (4-
2- (4-Allyloxyphenyl) ethanol was obtained from hydroxyphenyl) ethanol and allyl bromide. NMR (CDCl ₃ , δ): 1.40 (1H, t, J = 5Hz), 2.80
(2H, t, J = 7Hz), 3.82 (2H, m), 4.51 (2H, m), 5.28 (1H,
d, J = 9Hz), 5.40 (1H, d, J = 16Hz), 6.05 (1H, m), 6.87 (2
(H, d, J = 8Hz), 7.13 (2H, d, J = 8Hz)

(2) In the same manner as in Production Example 19- (4), 2- (4-allyloxyphenyl) ethyl iodide was obtained from 2- (4-allyloxyphenyl) ethanol. NMR (CDCl ₃ , δ): 3.11 (2H, t, J = 7Hz),
3.31 (2H, t, J = 7Hz), 4.52 (2H, m), 5.29 (1H, m), 5.40
(1H, m), 6.05 (1H, m), 6.87 (2H, d, J = 8Hz), 7.10 (2H,
d, J = 8Hz)

(3) In the same manner as in Production Example 1- (7),
From 2- (4-allyloxyphenyl) ethyl iodide and diethyl acetamidomalonate to 2-acetamido-2- [2- (4-allyloxyphenyl) ethyl]
Diethyl malonate was obtained. NMR (CDCl ₃ , δ): 1.24 (6H, t, J = 7Hz), 1.99
(3H, s), 2.42 (2H, m), 2.66 (2H, m), 4.20 (4H, q, J = 7H
z), 4.50 (1H, m), 5.28 (1H, d, J = 9Hz), 5.39 (1H, d, J = 1
6Hz), 6.03 (1H, m), 6.77 (1H, s), 6.82 (2H, d, J = 8Hz),
7.05 (2H, d, J = 8Hz)

(4) 2-acetamido-2- [2- (4
-Allyloxyphenyl) ethyl] malonate (2.0 g), tert-butyldimethylsilane (1.
85 g) and a 0.1 M solution of hexachloroplatinic (IV) acid in isopropanol (0.1 ml).
Stirred at 1.5 ° C for 1.5 hours. The reaction mixture was chromatographed on a silica gel column (hexane-ethyl acetate, 7: 3 as eluent) to give 2-acetamido-2-acetamide.
Diethyl [2- [4- [3- (tert-butyldimethylsilyl) propoxy] phenyl] ethyl] malonate (840 mg) was obtained as an oil. NMR (CDCl ₃ , δ): -0.03 (6H, s), 0.59 (2H,
m), 0.88 (9H, s), 1.25 (6H, t, J = 7Hz), 1.77 (2H, m),
1.99 (3H, s), 2.42 (2H, m), 2.65 (2H, m), 3.87 (2H, t,
J = 7Hz), 4.21 (4H, q, J = 7Hz), 6.76 (1H, s), 6.80 (2H,
d, J = 8Hz), 7.05 (2H, d, J = 8Hz)

Example 40 (1) In the same manner as in Example 1- (1), 2-acetamido-2- [2- [4- [3- (tert-butyldimethylsilyl) propoxy] phenyl] ethyl] From diethyl malonate to 2-acetamido-2- [2- [4- [3
-(Tert-Butyldimethylsilyl) propoxy] phenyl] ethyl] -1,3-propanediol was obtained. NMR (CDCl ₃ , δ): -0.04 (6H, s), 0.60 (2H,
m), 0.88 (9H, s), 1.77 (2H, m), 1.9-2.0 (5H, m), 2.60
(2H, m), 3.62 (2H, m), 3.75 (2H, t, J = 7Hz), 3.8-3.9
(4H, m), 5.84 (1H, s), 6.83 (2H, d, J = 8Hz), 7.11 (2H,
d, J = 8Hz)

(2) In the same manner as in Example 1- (2),
2-acetamido-2- [2- [4- [3- (tert
-Butyldimethylsilyl) propoxy] phenyl] ethyl] -1,3-propanediol to 2-amino-2-
[2- [4- [3- (tert-Butyldimethylsilyl) propoxy] phenyl] ethyl] -1,3-propanediol hydrochloride was obtained. NMR (DMSO-d ₆ , δ): -0.06 (6H, s), 0.58
(2H, m), 0.85 (9H, s), 1.6-1.8 (4H, m), 2.53 (2H, m),
3.51 (4H, d, J = 5Hz), 3.87 (2H, t, J = 7Hz), 5.37 (2H, t, J
= 5Hz), 6.82 (2H, d, J = 8Hz), 7.09 (2H, d, J = 8Hz), 7.85
(3H, br s)

Production Example 41 In the same manner as in Production Example 40- (4), diethyl 2-acetamido-2- [2- [4- (2-pentenyloxy) phenyl] ethyl] malonate and cyclohexyldimethylsilane were used. -Acetamide-2- [2- [4-
[3- (cyclohexyldimethylsilyl) propoxy]
There was obtained diethyl [phenyl] ethyl] malonate. NMR (CDCl ₃ , δ): -0.06 (6H, s), 0.52-0.66
(3H, m), 1.00-1.30 (6H, m), 1.24 (6H, t, J = 7Hz), 1.61-
1.81 (8H, m), 1.99 (3H, s), 2.37-2.46 (2H, m), 2.61-2.
70 (2H, m), 3.87 (2H, t, J = 7Hz), 4.21 (4H, q, J = 7Hz),
6.76 (1H, brs), 6.80 (2H, d, J = 8Hz), 7.04 (2H, d, J = 8H
z)

Example 41 (1) In the same manner as in Example 1- (1), 2-acetamido-2- [2- [4- [3- (cyclohexyldimethylsilyl) propoxy)] phenyl] ethyl] malon 2-acetamido-2- [2- [4- [3
-(Cyclohexyldimethylsilyl) propoxy] phenyl] ethyl] -1,3-propanediol was obtained. NMR (CDCl ₃ , δ): -0.06 (6H, s), 0.52-0.66
(3H, m), 0.99-1.27 (6H, m), 1.11-1.31 (6H, m), 1.88-
1.99 (2H, m), 1.96 (3H, s), 2.55-2.64 (2H, m), 3.57-
3.65 (2H, m), 3.68-3.75 (2H, m), 3.82-3.88 (2H, m),
3.87 (2H, t, J = 7Hz), 5.82 (1H, br s), 6.82 (2H, d, J = 8H
z), 7.08 (2H, d, J = 8Hz) ESI-MS: 434 (MH)

(2) In the same manner as in Example 1- (2),
From 2-acetamido-2- [2- [4- [3- (cyclohexyldimethylsilyl) propoxy] phenyl] ethyl] -1,3-propanediol to 2-amino-2-
[2- [4- [3- (cyclohexyldimethylsilyl)]
[Propoxy] phenyl] ethyl] -1,3-propanediol was obtained. NMR (DMSO-d ₆ , δ): -0.06 (6H, s), 0.52-
0.66 (3H, m), 0.98-1.30 (6H, m), 1.41-1.50 (2H, m), 1.
59-1.74 (6H, m), 2.47-2.55 (2H, m), 3.16-3.29 (4H, m),
3.86 (2H, t, J = 7Hz), 4.43 (2H, t, J = 5Hz), 6.80 (2H, d,
J = 8Hz), 7.06 (2H, d, J = 8Hz)

Production Example 42 (1) In the same manner as in Production Example 27- (5), 2- (4-
Hydroxyphenyl) ethanol and 4-bromo-1
2- [4- (3-Butenyloxy) phenyl] ethanol was obtained from -butene. NMR (CDCl ₃ , δ): 1.40 (1H, t, J = 5Hz), 2.53
(2H, m), 2.80 (2H, t, J = 7Hz), 3.82 (2H, m), 4.00 (2H, m
t, J = 7Hz), 5.05-5.2 (2H, m), 5.90 (1H, m), 6.87 (2H, d,
J = 8Hz), 7.13 (2H, d, J = 8Hz)

(2) In the same manner as in Production Example 19- (4), 2- [4- (3-butenyloxy) phenyl] ethyl iodide was obtained from 2- [4- (3-butenyloxy) phenyl] ethanol. NMR (CDCl ₃ , δ): 2.54 (2H, m), 3.10 (2H, t,
J = 7Hz), 3.31 (2H, t, J = 7Hz), 4.00 (2H, t, J = 7Hz), 5.05
-5.2 (2H, m), 5.90 (1H, m), 6.85 (2H, d, J = 8Hz), 7.10
(2H, d, J = 8Hz)

(3) In the same manner as in Production Example 1- (7),
2- [4- (3-butenyloxy) phenyl] ethyl
2- from iodide and diethyl acetamidomalonate
Diethyl acetamido-2- [2- [4- (3-butenyloxy) phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): 1.24 (6H, t, J = 7Hz), 1.99
(3H, s), 2.41 (2H, m), 2.52 (2H, m), 2.65 (2H, m), 3.9
8 (2H, t, J = 7Hz), 4.20 (4H, q, J = 7Hz), 5.05-5.2 (2H, m),
5.89 (1H, m), 6.74-6.83 (3H, m), 7.04 (2H, d, J = 8Hz)

(4) In the same manner as in Production Example 40- (4), diethyl 2-acetamido-2- [2- [4- (3-butenyloxy) phenyl] ethyl] malonate and tert-butyldimethylsilane were used. Diethyl 2-acetamido-2- [2- [4- [4- (tert-butyldimethylsilyl) butoxy] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): -0.07 (6H, s), 0.55 (2H,
m), 0.85 (9H, s), 1.24 (6H, t, J = 7Hz), 1.45 (2H, m),
1.78 (2H, m), 2.00 (3H, s), 2.42 (2H, m), 2.64 (2H, m)
m), 3.91 (2H, t, J = 7Hz), 4.29 (4H, q, J = 7Hz), 6.7-6.8
(3H, m), 7.03 (2H, d, J = 8Hz)

Example 42 (1) In the same manner as in Example 1- (1), 2-acetamido-2- [2- [4- [4- (tert-butyldimethylsilyl) butoxy] phenyl] ethyl] From diethyl malonate to 2-acetamido-2- [2- [4- [4-
(Tert-Butyldimethylsilyl) butoxy] phenyl] ethyl] -1,3-propanediol was obtained. NMR (CDCl ₃ , δ): -0.07 (6H, s), 0.55 (2H,
m), 0.85 (9H, s), 1.45 (2H, m), 1.78 (2H, m), 1.9-2.0
(5H, m), 2.60 (2H, m), 3.61 (2H, m), 3.74 (2H, m), 3.
8-3.95 (4H, m), 5.83 (1H, s), 6.82 (2H, d, J = 8Hz), 7.0
9 (2H, d, J = 8Hz)

(2) In the same manner as in Example 1- (2),
2-acetamido-2- [2- [4- [4- (tert
-Butyldimethylsilyl) butoxy] phenyl] ethyl] -1,3-propanediol to 2-amino-2-
[2- [4- [4- (tert-Butyldimethylsilyl) butoxy] phenyl] ethyl] -1,3-propanediol hydrochloride was obtained. NMR (DMSO-d ₆ , δ): -0.08 (6H, s), 0.53
(2H, m), 0.84 (9H, s), 1.42 (2H, m), 1.65-1.8 (4H, m),
2.53 (2H, m), 3.51 (4H, d, J = 5Hz), 3.91 (2H, t, J = 7H
z), 5.37 (2H, t, J = 5Hz), 6.82 (2H, d, J = 8Hz), 7.09 (2
(H, d, J = 8Hz), 7.83 (3H, br s)

Production Example 43 In a similar manner to Production Example 40- (4), diethyl 2-acetamido-2- [2- (4-allyloxyphenyl) ethyl] malonate and dimethylphenylsilane were used to prepare 2-
Diethyl acetamido-2- [2- [4- [3- (dimethylphenylsilyl) propoxy] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): 0.29 (6H, s), 0.85 (2H,
m), 1.24 (6H, t, J = 7Hz), 1.78 (2H, m), 1.99 (3H, s),
2.40 (2H, m), 2.65 (2H, m), 3.85 (2H, t, J = 7Hz), 4.20
(4H, q, J = 7Hz), 6.7-6.8 (3H, m), 7.02 (2H, d, J = 8Hz),
7.35 (3H, m), 7.51 (2H, m)

Example 43 (1) In the same manner as in Example 1- (1), 2-acetamido-2- [2- [4- [3- (dimethylphenylsilyl) propoxy] phenyl] ethyl] malonic acid From diethyl to 2-acetamido-2- [2- [4- [3- (dimethylphenylsilyl) propoxy] phenyl] ethyl]
-1,3-propanediol was obtained. NMR (CDCl ₃ , δ): 0.29 (6H, s), 0.85 (2H,
m), 1.78 (2H, m), 1.9-2.0 (5H, m), 2.59 (2H, m), 3.60
(2H, m), 3.75 (2H, t, J = 7Hz), 3.8-3.9 (4H, m), 5.83 (1
H, s), 6.78 (2H, d, J = 8Hz), 7.08 (2H, d, J = 8Hz), 7.36 (3
H, m), 7.51 (2H, m)

(2) In the same manner as in Example 1- (2),
2-acetamido-2- [2- [4- [3- (dimethylphenylsilyl) propoxy] phenyl] ethyl]-
From 1,3-propanediol, 2-amino-2- [2-
[4- [3- (dimethylphenylsilyl) propoxy]
[Phenyl] ethyl] -1,3-propanediol hydrochloride was obtained. NMR (DMSO-d ₆ , δ): 0.27 (6H, s), 0.82 (2
H, m), 1.6-1.8 (4H, m), 2.53 (2H, m), 3.51 (4H, d, J = 5H
z), 3.86 (2H, t, J = 7Hz), 5.39 (2H, t, J = 5Hz), 6.80 (2H, t, J = 5Hz)
(H, d, J = 8Hz), 7.09 (2H, d, J = 8Hz), 7.38 (3H, m), 7.51
(2H, m), 7.87 (3H, br s)

Production Example 44 In the same manner as in Production Example 40- (4), 2-acetamido-2- [2- [4- (3-butenyloxy) phenyl]
From ethyl [ethyl] malonate and dimethylphenylsilane, 2-acetamido-2- [2- [4- [4- (dimethylphenylsilyl) butoxy] phenyl] ethyl]
Diethyl malonate was obtained. NMR (CDCl ₃ , δ): 0.27 (6H, s), 0.79 (2H,
m), 1.24 (6H, t, J = 7Hz), 1.48 (2H, m), 1.78 (2H, m),
1.99 (3H, s), 2.40 (2H, m), 2.65 (2H, m), 3.89 (2H, t,
J = 7Hz), 4.20 (4H, q, J = 7Hz), 6.74-6.81 (3H, m), 7.02
(2H, d, J = 8Hz), 7.35 (3H, m), 7.50 (2H, m)

Example 44 (1) In the same manner as in Example 1- (1), 2-acetamido-2- [2- [4- [4- (dimethylphenylsilyl) butoxy] phenyl] ethyl] malonic acid From diethyl to 2-acetamido-2- [2- [4- [4- (dimethylphenylsilyl) butoxy] phenyl] ethyl]-
1,3-propanediol was obtained. NMR (CDCl ₃ , δ): 0.27 (6H, s), 0.80 (2H,
m), 1.49 (2H, m), 1.78 (2H, m), 1.9-2.0 (5H, m), 2.59
(2H, m), 3.60 (2H, m), 3.76 (2H, t, J = 7Hz), 3.8-3.95
(4H, m), 5.83 (1H, s), 6.80 (2H, d, J = 8Hz), 7.09 (2H,
d, J = 8Hz), 7.35 (3H, m), 7.50 (2H, m)

(2) In the same manner as in Example 1- (2),
2-acetamido-2- [2- [4- [4- (dimethylphenylsilyl) butoxy] phenyl] ethyl] -1,
From 3-propanediol to 2-amino-2- [2- [4
-[4- (Dimethylphenylsilyl) butoxy] phenyl] ethyl] -1,3-propanediol hydrochloride was obtained. NMR (DMSO-d ₆ , δ): 0.23 (6H, s), 0.78 (2
H, m), 1.41 (2H, m), 1.65-1.8 (4H, m), 2.53 (2H, m),
3.51 (4H, d, J = 5Hz), 3.89 (2H, t, J = 7Hz), 5.38 (2H, t, J
= 5Hz), 6.80 (2H, d, J = 8Hz), 7.09 (2H, d, J = 8Hz), 7.35
(3H, m), 7.50 (2H, m), 7.86 (3H, br s)

Production Example 45 (1) In the same manner as in Production Example 52- (5), 2- (4-
Allyloxyphenyl) ethyl iodide and diethyl malonate gave diethyl 2- [2- (4-allyloxyphenyl) ethyl] malonate. NMR (CDCl ₃ , δ): 1.27 (6H, t, J = 7Hz), 2.19
(2H, dt, J = 7,7Hz), 2.60 (2H, t, J = 7Hz), 3.33 (1H, t, J = 7H
z), 4.20 (4H, q, J = 7Hz), 4.51 (2H, d, J = 7Hz), 5.28 (1
H, d, J = 12Hz), 5.40 (1H, d, J = 16Hz), 6.05 (1H, ddt, J = 1
6,12,7Hz), 6.85 (2H, d, J = 8Hz), 7.10 (2H, d, J = 8Hz)

(2) In the same manner as in Production Example 40- (4), 2- [2- (4-allyloxyphenyl) ethyl]
From diethyl malonate and dimethyl (4-methylphenyl) silane, 2- [2- [4- [3- [dimethyl (4
-Methylphenyl) silyl] propoxy] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): 0.28 (6H, s), 0.83 (2H,
m), 1.25 (6H, t, J = 7Hz), 1.79 (2H, m), 2.18 (2H, m),
2.35 (3H, s), 2.59 (2H, m), 3.32 (1H, t, J = 7Hz), 3.85
(2H, t, J = 7Hz), 4.19 (4H, q, J = 7Hz), 6.77 (2H, d, J = 8H
z), 7.05 (2H, d, J = 8Hz), 7.18 (2H, d, J = 8Hz), 7.42 (2
(H, d, J = 8Hz)

(3) In the same manner as in Production Example 3- (6),
2- [2- [4- [3- [dimethyl (4-methylphenyl) silyl] propoxy)] phenyl] ethyl] malonate and O- (2,4-dinitrophenyl) hydroxylamine to give 2-amino-2 -[2- [4-
Diethyl [3- [dimethyl (4-methylphenyl) silyl] propoxy] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): 0.25 (6H, s), 0.82 (2H,
m), 1.28 (6H, t, J = 7Hz), 1.78 (2H, m), 2.02 (2H, br
s), 2.21 (2H, m), 2.35 (3H, s), 2.58 (2H, m), 3.85 (2
H, t, J = 7Hz), 4.22 (4H, q, J = 7Hz), 6.78 (2H, d, J = 8Hz),
7.09 (2H, d, J = 8Hz), 7.18 (2H, d, J = 8Hz), 7.41 (2H, d, J
= 8Hz)

Example 45 In the same manner as in Example 1- (1), 2-amino-2-
[2- [4- [3- [dimethyl (4-methylphenyl)
From diethyl [silyl] propoxy] phenyl] ethyl] malonate to 2-amino-2- [2- [4- [3- [dimethyl (4-methylphenyl) silyl] propoxy] phenyl] ethyl] -1,3-propanediol I got NMR (DMSO-d ₆ , δ): 0.25 (6H, s), 0.80 (2
H, m), 1.45 (2H, m), 1.50 (2H, m), 1.66 (2H, m), 2.30
(3H, s), 2.50 (2H, m), 3.23 (4H, m), 3.85 (2H, t, J = 7H
z), 4.45 (2H, br s), 6.77 (2H, d, J = 8Hz), 7.07 (2H, d,
J = 8Hz), 7.16 (2H, d, J = 8Hz), 7.42 (2H, d, J = 8Hz)

Production Example 46 (1) In the same manner as in Production Example 40- (4), 2- [2-
2- (2- [4- [3- [dimethyl (4-methoxyphenyl) silyl] propoxy] phenyl] ethyl] malon from diethyl (4-allyloxyphenyl) ethyl] malonate and dimethyl (4-methoxyphenyl) silane Diethyl acid was obtained. NMR (CDCl ₃ , δ): 0.25 (6H, s), 0.82 (2H,
m), 1.25 (6H, t, J = 7Hz), 1.77 (2H, m), 2.17 (2H, m),
2.59 (2H, m), 3.32 (1H, t, J = 7Hz), 3.81 (3H, s), 3.85
(2H, t, J = 7Hz), 4.19 (4H, q, J = 7Hz), 6.78 (2H, d, J = 8H
z), 6.90 (2H, d, J = 8Hz), 7.07 (2H, d, J = 8Hz), 7.43 (2
(H, d, J = 8Hz)

(2) In the same manner as in Production Example 3- (6),
From 2- [2- [4- [3- [dimethyl (4-methoxyphenyl) silyl] propoxy] phenyl] ethyl] malonate and O- (2,4-dinitrophenyl) hydroxylamine to 2-amino-2- [2- [4-
Diethyl [3- [dimethyl (4-methoxyphenyl) silyl] propoxy] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): 0.25 (6H, s), 0.82 (2H,
m), 1.28 (6H, t, J = 7Hz), 1.78 (2H, m), 2.03 (2H, br
s), 2.22 (2H, m), 2.58 (2H, m), 3.80 (3H, s), 3.85 (2
H, t, J = 7Hz), 4.22 (4H, q, J = 7Hz), 6.78 (2H, d, J = 8Hz),
6.91 (2H, d, J = 8Hz), 7.08 (2H, d, J = 8Hz), 7.43 (2H, d, J
= 8Hz)

Example 46 In the same manner as in Example 1- (1), 2-amino-2-
[2- [4- [3- [dimethyl (4-methoxyphenyl) silyl] propoxy] phenyl] ethyl] malonate is converted to 2-amino-2- [2- [4- [3- [dimethyl (4-methoxy Phenyl) silyl] propoxy]
[Phenyl] ethyl] -1,3-propanediol was obtained. NMR (DMSO-d ₆ , δ): 0.25 (6H, s), 0.80 (2
H, m), 1.36 (2H, m), 1.46 (2H, m), 1.67 (2H, m), 2.50
(2H, m), 3.24 (4H, m), 3.77 (3H, s), 3.86 (2H, t, J = 7H
z), 4.45 (2H, m), 6.77 (2H, d, J = 8Hz), 6.95 (2H, d, J = 8
Hz), 7.07 (2H, d, J = 8Hz), 7.45 (2H, d, J = 8Hz)

Production Example 47 (1) In the same manner as in Production Example 40- (4), 2- [2-
(4-allyloxyphenyl) ethyl] malonate and dimethyl (3-methylphenyl) silane
Diethyl-[2- [4- [3- [dimethyl (3-methylphenyl) silyl] propoxy] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): 0.28 (6H, s), 0.85 (2H,
m), 1.26 (6H, t, J = 7Hz), 1.79 (2H, m), 2.18 (2H, m),
2.35 (3H, s), 2.58 (2H, m), 3.31 (1H, t, J = 7Hz), 3.85
(2H, t, J = 7Hz), 4.19 (4H, q, J = 7Hz), 6.78 (2H, d, J = 8H
z), 7.06 (2H, d, J = 8Hz), 7.16 (1H, m), 7.26 (1H, m),
7.32 (2H, m)

(2) In the same manner as in Production Example 3- (6),
From 2- [2- [4- [3- [dimethyl (3-methylphenyl) silyl] propoxy] phenyl] ethyl] malonate and O- (2,4-dinitrophenyl) hydroxylamine to 2-amino-2- [2- [4- [3
-Diethyl [dimethyl (3-methylphenyl) silyl] propoxy] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): 0.28 (6H, s), 0.85 (2H,
m), 1.28 (6H, t, J = 7Hz), 1.79 (2H, m), 2.03 (2H, br
s), 2.22 (2H, m), 2.35 (3H, s), 2.60 (2H, m), 3.88 (2
(H, t, J = 7Hz), 4.23 (4H, q, J = 7Hz), 6.79 (2H, d, J = 8Hz),
7.09 (2H, d, J = 8Hz), 7.18 (1H, m), 7.26 (1H, m), 7.31
(2H, m)

Example 47 (1) In the same manner as in Example 1- (1), 2-amino-
From 2- [2- [4- [3- [dimethyl (3-methylphenyl) silyl] propoxy] phenyl] ethyl] malonate to 2-amino-2- [2- [4- [3- [dimethyl (3 -Methylphenyl) silyl] propoxy] phenyl] ethyl] -1,3-propanediol was obtained. NMR (DMSO-d ₆ , δ): 0.25 (6H, s), 0.80 (2
H, m), 1.29 (2H, br s), 1.45 (2H, m), 1.67 (2H, m), 2.3
0 (3H, s), 2.50 (2H, m), 3.23 (4H, m), 3.85 (2H, t, J = 7
Hz), 4.44 (2H, m), 6.75 (2H, d, J = 8Hz), 7.05 (2H, d, J =
8Hz), 7.17 (1H, m), 7.25 (1H, m), 7.30 (2H, m)

(2) In the same manner as in Example 26- (2), 2-amino-2- [2- [4- [3- [dimethyl (3-methylphenyl) silyl] propoxy] phenyl] ethyl] From 1,3-propanediol to 2-amino-2- [2- [4- [3- [dimethyl (3-methylphenyl) silyl] propoxy] phenyl] ethyl]-
1,3-propanediol hydrochloride was obtained. NMR (DMSO-d ₆ , δ): 0.25 (6H, s), 0.75 (2
H, m), 1.65 (2H, m), 1.75 (2H, m), 2.29 (3H, s), 2.53
(2H, m), 3.50 (4H, m), 3.85 (2H, t, J = 7Hz), 5.37 (2H, t,
J = 7Hz), 6.78 (2H, d, J = 8Hz), 7.08 (2H, d, J = 8Hz), 7.17
(1H, m), 7.25 (1H, m), 7.30 (2H, m), 7.85 (3H, br s)

Production Example 48 (1) In the same manner as in Production Example 40- (4), 2- [2-
2- (2- [4- [3- [dimethyl (3-methoxyphenyl) silyl] propoxy] phenyl] ethyl] malon from diethyl (4-allyloxyphenyl) ethyl] malonate and dimethyl (3-methoxyphenyl) silane Diethyl acid was obtained. NMR (CDCl ₃ , δ): 0.30 (6H, s), 0.85 (2H,
m), 1.27 (6H, t, J = 7Hz), 1.79 (2H, m), 2.18 (2H, m),
2.59 (2H, m), 3.33 (1H, t, J = 7Hz), 3.81 (3H, s), 3.86
(2H, t, J = 7Hz), 4.20 (4H, q, J = 7Hz), 6.78 (2H, d, J = 8H
z), 6.90 (1H, m), 7.07 (3H, m), 7.30 (2H, m)

(2) In the same manner as in Production Example 3- (6),
From 2- [2- [4- [3- [dimethyl (3-methoxyphenyl) silyl] propoxy] phenyl] ethyl] malonate and O- (2,4-dinitrophenyl) hydroxylamine to 2-amino-2- [2- [4-
Diethyl [3- [dimethyl (3-methoxyphenyl) silyl] propoxy] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): 0.29 (6H, s), 0.85 (2H,
m), 1.27 (6H, t, J = 7Hz), 1.78 (2H, m), 2.03 (2H, br
s), 2.21 (2H, m), 2.58 (2H, m), 3.81 (3H, s), 3.85 (2
H, t, J = 7Hz), 4.21 (4H, q, J = 7Hz), 6.77 (2H, d, J = 8Hz),
6.89 (1H, dd, J = 8,3Hz), 7.08 (4H, m), 7.30 (1H, d, J = 8H
z)

Example 48 In the same manner as in Example 1- (1), 2-amino-2-
[2- [4- [3- [dimethyl (3-methoxyphenyl) silyl] propoxy] phenyl] ethyl] malonate is converted to 2-amino-2- [2- [4- [3- [dimethyl (3-methoxy Phenyl) silyl] propoxy]
[Phenyl] ethyl] -1,3-propanediol hydrochloride was obtained. NMR (CDCl ₃ , δ): 0.25 (6H, s), 0.77 (2H,
m), 1.70 (2H, m), 1.93 (2H, m), 2.30 (2H, m), 2.53 (2
H, m), 3.73 (6H, m), 3.78 (3H, s), 6.69 (2H, m), 6.86
(1H, m), 7.03 (3H, m), 7.25 (2H, m), 7.83 (3H, br s)

Production Example 49 (1) To a solution of thiophene (20.8 g) in tetrahydrofuran (200 ml), 1.6 M butyllithium (hexane solution, 148 ml) was added over 30 minutes at -40 ° C. After stirring at −30 ° C. to −20 ° C. for 30 minutes, chlorodimethylsilane (21.3 g) in tetrahydrofuran (30 ml) was added at −10 ° C. or less over 30 minutes. The mixture was stirred overnight at room temperature. Thereafter, the resulting mixture was poured into water and separated. The organic layer was washed with brine, dried over magnesium sulfate and evaporated to dryness.
The residue is distilled to give dimethyl (2-thienyl) silane (4.
2 g) were obtained. NMR (CDCl ₃ , δ): 0.41 (6H, d, J = 5 Hz), 4.57
(1H, m), 7.21 (1H, m), 7.32 (1H, m), 7.63 (1H, m)

(2) In the same manner as in Production Example 40- (4), 2- [2- (4-allyloxyphenyl) ethyl]
Diethyl 2- [2- [4- [3- [dimethyl (2-thienyl) silyl] propoxy] phenyl] ethyl] malonate was obtained from diethyl malonate and dimethyl (2-thienyl) silane. NMR (CDCl ₃ , δ): 0.37 (6H, s), 0.84-0.94
(2H, m), 1.28 (6H, t, J = 7Hz), 1.76-1.89 (2H, m), 2.12-
2.25 (2H, m), 2.53-2.63 (2H, m), 3.32 (1H, t, J = 7Hz),
3.88 (2H, t, J = 7Hz), 4.20 (4H, q, J = 7Hz), 6.80 (2H, d, J
= 8Hz), 7.08 (2H, d, J = 8Hz), 7.21 (1H, m), 7.28 (1H,
m), 7.62 (1H, d, J = 5Hz)

(3) In the same manner as in Production Example 3- (6),
From 2- [2- [4- [3- [dimethyl (2-thienyl) silyl] propoxy] phenyl] ethyl] malonate and O- (2,4-dinitrophenyl) hydroxylamine to 2-amino-2- [ Diethyl 2- [4- [3- [dimethyl (2-thienyl) silyl] propoxy] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): 0.35 (6H, s), 0.84-0.93
(2H, m), 1.28 (6H, t, J = 7Hz), 1.73-1.88 (2H, m), 2.16-
2.26 (2H, m), 2.53-2.63 (2H, m), 3.87 (2H, t, J = 7Hz),
4.21 (4H, q, J = 7Hz), 6.78 (2H, d, J = 8Hz), 7.08 (2H, d, J
= 8Hz), 7.18 (1H, m), 7.27 (1H, m), 7.61 (1H, d, J = 3Hz) ESI-MS: 478 (M + H), 500 (M + Na)

Example 49 In the same manner as in Example 1- (1), 2-amino-2-
[2- [4- [3- [dimethyl (2-thienyl) silyl] propoxy] phenyl] ethyl] malonate is converted to diethyl 2-amino-2- [2- [4- [3- [dimethyl (2-thienyl) [Silyl] propoxy] phenyl] ethyl] -1,3-propanediol was obtained. NMR (CDCl ₃ -CD ₃ OD, δ): 0.34 (6H, s),
0.82-0.93 (2H, m), 1.58-1.69 (2H, m), 1.75-1.89 (2
H, m), 2.49-2.62 (2H, m), 3.43-3.51 (2H, m), 3.53-3.6
5 (2H, m), 3.87 (3H, t, J = 7Hz), 6.78 (2H, d, J = 8Hz), 7.
08 (2H, d, J = 8Hz), 7.19 (1H, m), 7.28 (1H, m), 7.62 (1
(H, d, J = 5Hz)

Production Example 50 (1) 2- (hydroxymethyl) -2-nitro-1,3
-Propanediol (45 g) was heated in acetone (6
5 ml) and cooled to 15-20 ° C. To this solution was added boron trifluoride diethyl ether complex (36.6 m
l) was added and stirred at room temperature for 5 minutes. The mixture was poured into ice-cooled saturated aqueous sodium hydrogen carbonate solution (350 ml) and stirred for 15 minutes. The insoluble salts were collected by filtration, washed with cold water (200 ml × 3), dried under reduced pressure,
2-dimethyl-5-hydroxymethyl-5-nitro-
1,3-Dioxane (44.6 g) was obtained. NMR (CDCl ₃ , δ): 1.42 (3H, s), 1.44 (3H,
s), 2.12 (1H, t, J = 6Hz), 4.04 (2H, d, J = 11Hz), 4.07 (2
(H, d, J = 6Hz), 4.39 (2H, d, J = 11Hz)

(2) 2,2-dimethyl-5-hydroxymethyl-5-nitro-1,3-dioxane (2.0 g)
And pyridine (1.27 ml) in dichloromethane (3
Trifluoromethanesulfonic anhydride (2.1 ml) was added to the cooled solution in 0 ml) over 30 minutes. The mixture is stirred for 20 minutes below 9 ° C., then
The mixture was poured into ice water and separated. The organic solution was concentrated under reduced pressure, dissolved in ethyl acetate (40 ml), water (20 ml × 2),
The extract was washed successively with a saturated aqueous sodium hydrogen carbonate solution (20 ml × 2) and brine (20 ml). After drying over magnesium sulfate, the organic solution was evaporated and the crude 2,2-dimethyl-5-nitro-5-[(trifluoromethylsulfonyloxy) methyl] -1,3-dioxane (3.4
2 g) were obtained. This was used for the next step without further purification. NMR (CDCl ₃ , δ): 1.43 (3H, s), 1.49 (3H,
s), 4.06 (2H, d, J = 13Hz), 4.39 (2H, d, J = 13Hz), 5.04 (2
H, s)

(3) 1- (p-toluenesulfonyloxy) -5 was added to a solution of hydroquinone (6.25 g) and potassium hydroxide (2.5 g) in a methanol-ethanol mixture (1: 5, 50 ml). -(Trimethylsilyl)
Pentane (3.19 g) was added at 65 ° C. over 90 minutes. The mixture was stirred at 65 ° C. for 30 minutes, after which
Stirred at 80 ° C. for 6 hours. After cooling, the insoluble salts are filtered off,
The liquid was evaporated to dryness. The residue was dissolved in ethyl acetate (80 ml), water (50 ml × 2), 0.1N hydrochloric acid (50 ml).
1), water (50 ml) and brine (50 ml) sequentially. The organic solution was dried over magnesium sulfate, concentrated under reduced pressure, and mixed with ethyl acetate-hexane (10: 1).
Was purified on a silica gel column (80 cc) using as an eluent to obtain 4- [5- (trimethylsilyl) pentyloxy] phenol (1.99 g). NMR (CDCl ₃ , δ): -0.02 (9H, s), 0.47-0.54
(2H, m), 1.29-1.51 (4H, m), 1.70-1.81 (2H, m), 3.89
(2H, t, J = 7Hz), 4.47 (1H, brs), 6.71-6.81 (4H, m) ESI-MS: 251 (MH)

(4) A cooled solution of 4- [5- (trimethylsilyl) pentyloxy] phenol (1.78 g) and potassium carbonate (4.87 g) in N, N-dimethylformamide (10 ml) was added with 2-dimethyl-
5-Nitro-5-[(trifluoromethylsulfonyloxy) methyl] -1,3-dioxane (3.42 g) was added. After stirring at room temperature for 5 hours, 2,2-dimethyl-5-nitro-5-[(trifluoromethylsulfonyloxy) methyl] -1,3-dioxane (0.68 g)
Was added and the mixture was stirred at room temperature overnight. The obtained mixture was poured into ice water (100 ml), and ethyl acetate (60 ml) was added.
ml), extracted with water (50 ml × 2) and brine (5 ml).
0 ml). The organic solution was dried over magnesium sulfate and concentrated under reduced pressure. The residue was ethyl acetate-
The mixture was purified on a silica gel column (200 cc) using a hexane mixture (20: 1 to 10: 1) as an eluent.
2-dimethyl-5-nitro-5- [4- [5- (trimethylsilyl) pentyloxy] phenoxymethyl]-
1,3-Dioxane (2.63 g) was obtained. NMR (CDCl ₃ , δ): -0.03 (9H, s), 0.46-0.54
(2H, m), 1.26-1.50 (4H, m), 1.43 (3H, s), 1.44 (3H,
s), 1.72-1.85 (2H, m), 3.89 (2H, t, J = 7Hz), 4.15 (2H, m
d, J = 13Hz), 4.36 (2H, s), 4.47 (2H, d, J = 13Hz), 6.83
(4H, s)

(5) 2,2-dimethyl-5-nitro-5
-[4- [5- (trimethylsilyl) pentyloxy]
[Phenoxymethyl] -1,3-dioxane (1.50
g), iron powder (787 mg) and ammonium chloride (1.51 g) in a mixture of ethanol-water (3: 1, 3
0 ml) was heated at 90 ° C. for 3 hours. The hot mixture was filtered through Celite® and the residue was washed well with chloroform. The filtrate and the washings were combined, separated, and the organic solution was washed successively with water (50 ml) and a saturated aqueous sodium hydrogen carbonate solution (50 ml). The organic solution was dried over magnesium sulfate and evaporated to dryness. The residue was purified on a silica gel column (60 cc) using 0-2% methanol (in chloroform) as eluent,
-Amino-2,2-dimethyl-5- [4- [5- (trimethylsilyl) pentyloxy] phenoxymethyl]-
1,3-Dioxane (1.33 g) was obtained. NMR (CDCl ₃ , δ): -0.03 (9H, s), 0.45-0.54
(2H, m), 1.28-1.50 (4H, m), 1.41 (3H, s), 1.46 (3H,
s), 1.66-1.80 (2H, m), 3.61 (2H, d, J = 12Hz), 3.83-3.9
4 (6H, m), 6.77-6.94 (4H, m) ESI-MS: 396 (M + H)

Example 50 5-Amino-2,2-dimethyl-5- [4- [5- (trimethylsilyl) pentyloxy] phenyloxymethyl] -1,3-dioxane (1.41 g) in methanol (5 ml) The solution was added to a 3N aqueous hydrochloric acid solution (5 m
l) was added. After stirring at room temperature for 4 hours, the solution was added to a 1N aqueous sodium hydroxide solution (15 ml) in an ice water bath.
Neutralized. The resulting mixture was diluted with a saturated aqueous solution of sodium hydrogen carbonate (50 ml) and ethyl acetate (50 ml)
Extracted. The organic layer was washed with brine (50 ml), dried over magnesium sulfate and evaporated to dryness. The residue was recrystallized from ethyl acetate (5 ml) to give 2-amino-2.
-[4- [5- (trimethylsilyl) pentyloxy]
[Phenyloxymethyl] -1,3-propanediol (834 mg) was obtained. 2-amino-2- [4- [5-
To a cooled solution of a mixture of (trimethylsilyl) pentyloxy] phenyloxymethyl] -1,3-propanediol (500 mg) in methanol (2 ml) and dioxane (2 ml), 4N hydrogen chloride (dioxane solution, 1 ml) Was added. The solution was evaporated to dryness and the residue was recrystallized from ethyl acetate to give 2-amino-2- [4
-[5- (Trimethylsilyl) pentyloxy] phenyloxymethyl] -1,3-propanediol hydrochloride (462 mg) was obtained. NMR (DMSO-d ₆ , δ): -0.01 (9H, s), 0.47-
0.56 (2H, m), 1.28-1.49 (4H, m), 1.13-1.26 (2H, m), 3.
63 (4H, d, J = 5Hz), 3.80 (2H, t, J = 7Hz), 3.99 (2H, s),
5.44 (2H, t, J = 5Hz), 6.85-6.95 (4H, m), 8.07 (2H, br
s) ESI-MS: 356 (M + H)

Production Example 51 (1) 6- (Trimethylsilyl) hexyl iodide was obtained from 6- (trimethylsilyl) hexylmethanesulfonate in the same manner as in Production Example 1- (6). NMR (CDCl ₃ , δ): -0.02 (9H, s), 0.48 (2H,
m), 1.2-1.5 (6H, m), 1.81 (2H, m), 3.19 (2H, t, J = 7Hz)

(2) In the same manner as in Production Example 3- (2),
2- [4- [6- (Trimethylsilyl) hexyl] phenoxy] tetrahydropyran was obtained from 6- (trimethylsilyl) hexylmagnesium iodide and 2- (4-bromophenoxy) tetrahydropyran. NMR (CDCl ₃ , δ): -0.03 (9H, s), 0.47 (2H,
m), 1.2-2.1 (14H, m), 2.55 (2H, t, J = 7Hz), 3.59 (1H,
m), 3.94 (1H, m), 5.38 (1H, m), 6.97 (2H, d, J = 8Hz),
7.08 (2H, d, J = 8Hz)

(3) 2- in methanol (250 ml)
A mixture of [4- [6- (trimethylsilyl) hexyl] phenoxy] tetrahydropyran (4.64 g) and a 5% oxalic acid aqueous solution (27.5 ml) was stirred at room temperature for 5 hours. The mixture was concentrated, water was added and extracted with ethyl acetate. The organic solution was washed with brine, dried over magnesium sulfate and concentrated. The residue was purified on a silica gel column [15%
Ethyl acetate (in hexane)] to give 4- [6- (trimethylsilyl) hexyl] phenol (3.64 g) as an oil. NMR (DMSO-d ₆ , δ): -0.04 (9H, s), 0.45
(2H, m), 1.2-1.35 (6H, m), 1.48 (2H, m), 2.44 (2H, t, J
= 7Hz), 6.65 (2H, d, J = 8Hz), 6.95 (2H, d, J = 8Hz), 9.08
(1H, s)

(4) In the same manner as in Production Example 50- (4), 4- [6- (trimethylsilyl) hexyl] phenol and 2,2-dimethyl-5-nitro-5-[(trifluoromethylsulfonyloxy ) Methyl] -1,3
2,2-dimethyl-5-nitro-5 from dioxane
[4- [6- (Trimethylsilyl) hexyl] phenoxymethyl] -1,3-dioxane was obtained. NMR (CDCl ₃ , δ): -0.03 (9H, s), 0.47 (2H,
m), 1.2-1.4 (6H, m), 1.48 (3H, s), 1.50 (3H, s), 1.56
(2H, m), 2.54 (2H, t, J = 7Hz), 4.17 (2H, d, J = 13Hz), 4.
40 (2H, s), 4.49 (2H, d, J = 13Hz), 6.80 (2H, d, J = 8Hz),
7.09 (2H, d, J = 8Hz)

(5) In the same manner as in Production Example 50- (5), 2,2-dimethyl-5-nitro-5- [4- [6-
(Trimethylsilyl) hexyl] phenoxymethyl]-
From 1,3-dioxane, 5-amino-2,2-dimethyl-5- [4- [6- (trimethylsilyl) hexyl] phenoxymethyl] -1,3-dioxane was obtained. NMR (DMSO-d ₆ , δ): -0.04 (9H, s), 0.45
(2H, m), 1.2-1.35 (9H, m), 1.39 (3H, s), 1.50 (2H, m),
1.66 (2H, s), 2.48 (2H, m), 3.56 (2H, d, J = 11Hz), 3.6
7 (2H, d, J = 11Hz), 3.90 (2H, s), 6.86 (2H, d, J = 8Hz),
7.08 (2H, d, J = 8Hz)

Example 51 In the same manner as in Example 50, 5-amino-2,2-dimethyl-5- [4- [6- (trimethylsilyl) hexyl] phenoxymethyl] -1,3-dioxane was converted into 2-
Amino-2- [4- [6- (trimethylsilyl) hexyl] phenoxymethyl] -1,3-propanediol hydrochloride was obtained. NMR (DMSO-d ₆ , δ): -0.03 (9H, s), 0.46
(2H, m), 1.2-1.35 (6H, m), 1.52 (2H, m), 2.50 (2H, m),
3.64 (4H, d, J = 5Hz), 4.03 (2H, s), 5.46 (2H, t, J = 5H
z), 6.87 (2H, d, J = 8Hz), 7.12 (2H, d, J = 8Hz), 8.10 (3
H, br s)

Production Example 52 (1) 2- (4-Bromophenyl) ethanol (140 g), 3,4-dihydro-2H-pyran (70 g) in chloroform (280 ml) and pyridinium p-toluenesulfonate (8. 74g) was stirred at room temperature for 2 hours. The reaction mixture was washed sequentially with 1N hydrochloric acid and a saturated aqueous solution of sodium hydrogen carbonate, and dried over magnesium sulfate.
After evaporating the solvent, the crude residue was distilled under addition of sodium carbonate under reduced pressure to obtain 2- [2- (4-bromophenyl) ethoxy] tetrahydropyran (180 g). NMR (CDCl ₃ , δ): 1.55 (4H, m), 1.70 (1H,
m), 1.80 (1H, m), 2.85 (2H, t, J = 7Hz), 3.45 (1H, m),
3.59 (1H, m), 3.73 (1H, m), 3.92 (1H, m), 4.58 (1H,
m), 7.12 (2H, d, J = 8Hz), 7.39 (2H, d, J = 8Hz)

(2) To a suspension of magnesium (852 mg) in tetrahydrofuran (100 ml) was added 2- [2-
(4-Bromophenyl) ethoxy] tetrahydropyran (10.0 g) was added dropwise, and the solution was refluxed for 1 hour. To this solution was added 5-bromo-1-pentene (627 mg) and dilithium tetrachlorocuprate at -78 ° C in tetrahydrofuran (3.51 ml) and the mixture was stirred at room temperature overnight. The mixture was poured into 1N hydrochloric acid and extracted with ethyl acetate. The organic layer was washed successively with water, a saturated aqueous solution of sodium hydrogen carbonate and brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate: hexane = 1: 19) to give 2- [2- [4- (4-pentenyl) phenyl].
[Ethoxy] tetrahydropyran (3.95 g) was obtained. NMR (CDCl ₃ , δ): 1.4-1.9 (8H, m), 2.02-2.1
(2H, m), 2.5-2.6 (2H, m), 2.82-2.90 (2H, m), 3.42-3.
50 (1H, m), 3.58-3.66 (1H, m), 3.72-3.80 (1H, m), 3.9
-4.0 (1H, m), 4.58 (1H, m), 4.9-5.05 (2H, m), 5.75-5.
90 (1H, m), 7.12 (4H, ABq)

(3) 2- [2- [4- (4-pentenyl) phenyl] ethoxy] tetrahydropyran (3.9
5g) in methanol (40 ml) was added to (1R)-
(-)-10-Camphorsulfonic acid (334 mg) was added at room temperature. After stirring at room temperature for 2 hours, the solvent was distilled off under reduced pressure, the residue was dissolved in ethyl acetate, washed sequentially with water, saturated aqueous sodium hydrogen carbonate solution and brine, dried over magnesium sulfate, and concentrated under reduced pressure. Then, 2- [4-
(4-pentenyl) phenyl] ethanol (2.98
g) was obtained. NMR (CDCl ₃ , δ): 1.62-1.74 (2H, m), 2.02-
2.12 (2H, m), 2.54-2.62 (2H, m), 2.8-2.9 (2H, m), 3.76
-3.88 (2H, m), 4.9-5.02 (2H, m), 5.76-5.9 (1H, m), 7.
1-7.18 (4H, m)

(4) 2- [4- (4-pentenyl) phenyl] ethanol (2.98 g) and iodine (6.5)
To a solution of 3g) in a mixture of ether (20ml) and acetonitrile (10ml) was added triphenylphosphine (6.26g) at room temperature. After stirring at room temperature for 2 hours, the solvent was distilled off under reduced pressure, the residue was dissolved in ethyl acetate, washed successively with a saturated aqueous solution of sodium hydrogen carbonate and brine, dried over magnesium sulfate, and concentrated under reduced pressure. , 2- [4- (4-pentenyl) phenyl] ethyl
Iodide (4.24 g) was obtained. NMR (CDCl ₃ , δ): 1.65-1.75 (2H, m), 2.04-
2.12 (2H, m), 2.56-2.62 (2H, m), 3.1-3.2 (2H, m), 3.3-
3.38 (2H, m), 4.94-5.06 (2H, m), 5.76-5.9 (1H, m), 7.
06-7.14 (4H, m)

(5) To a suspension of sodium hydride (676 mg) in N, N-dimethylformamide (43 ml),
Diethyl malonate (3.39 g) was added at room temperature and the mixture was stirred for 30 minutes. To this solution was added 2- [4- (4-pentenyl) phenyl] ethyl iodide (4.23 g) at 0 ° C and the mixture was stirred at room temperature for 2 hours. The mixture was poured into 1N hydrochloric acid, extracted with ethyl acetate, and the organic layer was extracted with water,
The extract was washed successively with a saturated aqueous solution of sodium hydrogen carbonate and brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography (200 m
1, ethyl acetate: hexane = 1: 19) to give diethyl 2- [2- [4- (4-pentenyl) phenyl] ethyl] malonate (2.49 g). NMR (CDCl ₃ , δ): 1.26 (6H, t, J = 7.5Hz), 1.6
8-1.76 (2H, m), 2.04-2.12 (2H, m), 2.16-2.24 (2H, m),
2.54-2.64 (4H, m), 3.32 (1H, t, J = 7.0Hz), 4.2 (4H, q, J
= 7.5Hz), 4.9-5.05 (2H, m), 5.76-5.88 (1H, m), 7.05-
7.10 (4H, m)

(6) In the same manner as in Production Example 40- (4), 2- [2- [4- [5- [5] was obtained from diethyl 2- [2- [4- (4-pentenyl) phenyl] ethyl] malonate. −
[Dimethyl (3,3,3-trifluoropropyl) silyl] pentyl] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): 0.02 (6H, s), 0.53 (2H,
m), 0.71 (2H, m), 1.25 (6H, t, J = 7Hz), 1.33 (4H, m),
1.61 (2H, m), 2.00 (2H, m), 2.20 (2H, m), 2.58 (2H,
m), 2.63 (2H, m), 3.35 (1H, t, J = 7Hz), 4.20 (4H, q, J = 7
Hz), 7.10 (4H, s)

(7) In the same manner as in Production Example 3- (6),
From 2- [2- [4- [5- [dimethyl (3,3,3-trifluoropropyl) silyl] pentyl] phenyl] ethyl] malonate to 2-amino-2- [2- [4
Diethyl-[5- [dimethyl (3,3,3-trifluoropropyl) silyl] pentyl] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): 0.00 (6H, s), 0.52 (2H,
m), 0.71 (2H, m), 1.28 (6H, t, J = 7Hz), 1.32 (4H, m),
1.59 (2H, m), 1.99 (2H, m), 2.03 (2H, m), 2.25 (2H, m
m), 2.57 (2H, m), 2.64 (2H, m), 4.22 (4H, q, J = 7Hz),
7.10 (4H, s)

Example 52 In the same manner as in Example 1- (1), 2-amino-2-
[2- [4- [5- [dimethyl (3,3,3-trifluoropropyl) silyl] pentyl] phenyl] ethyl]
From diethyl malonate to 2-amino-2- [2- [4-
[5- [dimethyl (3,3,3-trifluoropropyl) silyl] pentyl] phenyl] ethyl] -1,3-
Propanediol was obtained. NMR (DMSO-d ₆ , δ): -0.02 (6H, s), 0.50
(2H, m), 0.63 (2H, m), 1.30 (6H, m), 1.46 (2H, m), 1.5
3 (2H, m), 2.13 (2H, m), 2.50 (4H, m), 3.22 (4H, m),
4.43 (2H, m), 7.06 (4H, s)

Production Example 53 (1) In the same manner as in Production Example 52- (2), 2- [2-
2- [2- [4- (3-Butenyl) phenyl] ethoxy] tetrahydropyran was obtained from (4-bromophenyl) ethoxy] tetrahydropyran. NMR (CDCl ₃ , δ): 1.4-1.9 (6H, m), 2.3-2.4
(2H, m), 2.6-2.7 (2H, m), 2.86-2.90 (2H, m), 3.42-3.5
0 (1H, m), 3.58-3.66 (1H, m), 3.72-3.80 (1H, m), 3.9-
4.0 (1H, m), 4.6 (1H, m), 5.02-5.10 (2H, m), 5.9-6.05
(1H, m), 7.12 (4H, ABq)

(2) Preparation of 2- [2- [4- (3-butenyl) phenyl] ethoxy] tetrahydropyran from 2- [4- (3-butenyl) phenyl ] Ethanol was obtained. NMR (CDCl ₃ , δ): 2.32-2.4 (2H, m), 2.62-2.
70 (2H, m), 2.8-2.9 (2H, m), 3.7-3.8 (2H, m), 4.9-5.0
2 (2H, m), 5.78-5.9 (1H, m), 7.1-7.18 (4H, m)

(3) In the same manner as in Production Example 52- (4), 2- [4- (3-butenyl) phenyl] ethyl iodide was obtained from 2- [4- (3-butenyl) phenyl] ethanol. . NMR (CDCl ₃ , δ): 2.3-2.4 (2H, m), 2.54-2.6
2 (2H, m), 3.1-3.2 (2H, m), 3.3-3.4 (2H, m), 4.9-5.02
(2H, m), 5.75-5.9 (1H, m), 7.06-7.2 (4H, m)

(4) In the same manner as in Preparation Example 52- (5), 2- [4- (3-butenyl) phenyl] ethyl iodide was converted to 2- [2- [4- (3-butenyl) phenyl] ethyl. ] Diethyl malonate was obtained. NMR (CDCl ₃ , δ): 1.26 (6H, t, J = 7.5Hz), 2.1
6-2.24 (2H, m), 2.3-2.4 (2H, m), 2.6-2.7 (4H, m), 3.32
(1H, t, J = 7.0Hz), 4.18 (4H, q, J = 7.5Hz), 4.9-5.02 (2
H, m), 5.76-5.9 (1H, m), 7.05-7.1 (4H, m)

(5) In the same manner as in Production Example 40- (4), diethyl 2- [2- [4- (3-butenyl) phenyl] ethyl] malonate was used to give 2- [2- [4- [4 -Diethyl [[dimethyl (3-methoxybenzyl) silyl] butyl] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): 0.03 (6H, s), 0.59 (2H,
m), 1.30 (6H, t, J = 7Hz), 1.39 (2H, m), 1.64 (2H, m),
2.25 (2H, m), 2.60 (2H, m), 2.68 (2H, m), 3.39 (1H, t,
J = 7Hz), 3.80 (3H, s), 4.23 (4H, q, J = 7Hz), 6.60 (3H,
m), 7.12 (4H, s), 7.16 (1H, dd, J = 8,8Hz)

(6) In the same manner as in Production Example 3- (6),
From 2- [2- [4- [4- [dimethyl (3-methoxybenzyl) silyl] butyl] phenyl] ethyl] malonate diethyl to 2-amino-2- [2- [4- [4- [dimethyl (3 -Dimethoxybenzyl) silyl] butyl] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): 0.03 (6H, s), 0.58 (2H,
m), 1.32 (6H, t, J = 7Hz), 1.38 (2H, m), 1.64 (2H, m),
2.10 (4H, br s), 2.29 (2H, m), 2.60 (2H, m), 2.65 (2H, m
m), 3.81 (3H, s), 4.26 (4H, q, J = 7Hz), 6.60 (3H, m),
7.12 (4H, s), 7.17 (1H, m)

Example 53 In the same manner as in Example 1- (1), 2-amino-2-
From 2- [2- [4- [4- [dimethyl (3-methoxybenzyl) silyl] butyl] phenyl] ethyl] malonate to 2-amino-2- [2- [4- [4- [dimethyl (3-methoxy [Benzyl] silyl] butyl] phenyl] ethyl] -1,3-propanediol was obtained. NMR (DMSO-d ₆ , δ): -0.09 (6H, s), 0.50
(2H, m), 1.26 (4H, m), 1.46 (2H, m), 1.51 (2H, m), 2.0
3 (2H, s), 2.50 (4H, m), 3.22 (4H, m), 3.70 (3H, s),
4.43 (2H, m), 6.52 (2H, m), 6.60 (1H, m), 7.06 (5H, m)

Production Example 54 (1) In the same manner as in Production Example 40- (4), 2- [2-
Diethyl [4- [3- (ethylmethylphenylsilyl) propoxy] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): 0.29 (3H, s), 0.80 (2H, q,
J = 7Hz), 0.88 (2H, m), 0.98 (3H, t, J = 7Hz), 1.26 (6H,
t, J = 7Hz), 1.79 (2H, m), 2.18 (2H, m), 2.59 (2H, m),
3.33 (1H, t, J = 7Hz), 3.88 (2H, t, J = 7Hz), 4.20 (4H, q, J
= 7Hz), 6.78 (2H, d, J = 8Hz), 7.07 (2H, d, J = 8Hz), 7.35
(3H, m), 7.50 (2H, m)

(2) In the same manner as in Production Example 3- (6),
Diethyl 2-amino-2- [2- [4- [3- (ethylmethylphenylsilyl) propoxy] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): 0.29 (3H, s), 0.80 (2H,
m), 0.87 (2H, m), 0.98 (3H, m), 1.25 (6H, t, J = 7Hz),
1.78 (2H, m), 2.03 (2H, br s), 2.22 (2H, m), 2.59 (2H, m
m), 3.85 (2H, t, J = 7Hz), 4.22 (4H, q, J = 7Hz), 6.78 (2
(H, d, J = 8Hz), 7.09 (2H, d, J = 8Hz), 7.37 (3H, m), 7.50
(2H, m)

Example 54 In the same manner as in Example 1- (1), 2-amino-2-
[2- [4- [3- (Ethylmethylphenylsilyl) propoxy] phenyl] ethyl] -1,3-propanediol was obtained. NMR (DMSO-d ₆ , δ): 0.25 (3H, s), 0.7-0.9
5 (7H, m), 1.30 (2H, brs), 1.45 (2H, m), 1.65 (2H, m),
2.50 (2H, m), 3.22 (4H, m), 3.85 (2H, t, J = 7Hz), 4.42
(2H, m), 6.75 (2H, d, J = 8Hz), 7.03 (2H, d, J = 8Hz), 7.3
5 (3H, m), 7.50 (2H, m)

Production Example 55 (1) In the same manner as in Production Example 40- (4), 2- [2-
Diethyl [4- [3- (4-chlorophenyl) dimethylsilylpropoxy] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): 0.28 (6H, s), 0.84 (2H,
m), 1.26 (6H, t, J = 7Hz), 1.75 (2H, m), 2.18 (2H, m),
2.58 (2H, m), 3.32 (1H, t, J = 7Hz), 3.85 (2H, m), 4.20
(4H, q, J = 7Hz), 6.78 (2H, d, J = 8Hz), 7.07 (2H, d, J = 8H
z), 7.32 (2H, d, J = 8Hz), 7.42 (2H, d, J = 8Hz)

(2) In the same manner as in Production Example 3- (6),
2-amino-2- [2- [4- [3- (4-chlorophenyl) dimethylsilylpropoxy] phenyl] ethyl]
Diethyl malonate was obtained. NMR (CDCl ₃ , δ): 0.27 (6H, s), 0.83 (2H,
m), 1.27 (6H, t, J = 7Hz), 1.75 (2H, m), 2.02 (2H, br
s), 2.21 (2H, m), 2.59 (2H, m), 3.85 (2H, t, J = 7Hz), 4.
20 (4H, q, J = 7Hz), 6.77 (2H, d, J = 8Hz), 7.08 (2H, d, J = 8
Hz), 7.32 (2H, d, J = 8Hz), 7.43 (2H, d, J = 8Hz)

Example 55 In the same manner as in Example 1- (1), 2-amino-2-
[2- [4- [3- (4-Chlorophenyl) dimethylsilylpropoxy] phenyl] ethyl] -1,3-propanediol was obtained. NMR (DMSO-d ₆ , δ): 0.25 (6H, s), 0.80 (2
H, m), 1.25 (2H, br s), 1.44 (2H, m), 1.63 (2H, m), 2.5
0 (2H, m), 3.20 (4H, m), 3.32 (2H, t, J = 7Hz), 4.40 (2
H, m), 6.75 (2H, d, J = 8Hz), 7.05 (2H, d, J = 8Hz), 7.40
(2H, d, J = 8Hz), 7.50 (2H, d, J = 8Hz)

Production Example 56 (1) In the same manner as in Production Example 40- (4), 2- [2-
Diethyl [4- [3- (3-chlorophenyl) dimethylsilylpropoxy] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): 0.29 (6H, s), 0.85 (2H,
m), 1.25 (6H, t, J = 7Hz), 1.77 (2H, m), 2.18 (2H, m),
2.58 (2H, dd, J = 7,7Hz), 3.32 (1H, t, J = 7Hz), 3.85 (2H,
t, J = 7Hz), 4.18 (4H, q, J = 7Hz), 6.76 (2H, d, J = 8Hz), 7.
06 (2H, d, J = 8Hz), 7.30 (2H, m), 7.36 (1H, m), 7.45 (1
H, s)

(2) In the same manner as in Production Example 3- (6),
2-amino-2- [2- [4- [3- (3-chlorophenyl) dimethylsilylpropoxy] phenyl] ethyl]
Diethyl malonate was obtained. NMR (CDCl ₃ , δ): 0.29 (6H, s), 0.85 (2H,
m), 1.27 (6H, t, J = 7Hz), 1.75 (2H, m), 2.03 (2H, m),
2.22 (2H, m), 2.59 (2H, m), 3.85 (2H, t, J = 7Hz), 4.21
(4H, q, J = 7Hz), 6.78 (2H, d, J = 8Hz), 7.08 (2H, d, J = 8H
z), 7.25-7.40 (3H, m), 7.45 (1H, m)

Example 56 In the same manner as in Example 1- (1), 2-amino-2-
[2- [4- [3- (3-Chlorophenyl) dimethylsilylpropoxy] phenyl] ethyl] -1,3-propanediol was obtained. NMR (DMSO-d ₆ , δ): 0.27 (6H, s), 0.82 (2
H, m), 1.25 (2H, brs), 1.43 (2H, m), 1.65 (2H, m), 2.5
0 (2H, m), 3.20 (4H, m), 3.85 (2H, t, J = 7Hz), 4.42 (2
H, m), 6.76 (2H, d, J = 8Hz), 7.10 (2H, d, J = 8Hz), 7.35-
7.50 (4H, m)

Production Example 57 (1) In the same manner as in Production Example 40- (4), 2- [2-
Diethyl [4- [3- [dimethyl (2-methylphenyl) silyl] propoxy] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): 0.34 (6H, s), 0.94 (2H,
m), 1.28 (6H, t, J = 7Hz), 1.75 (2H, m), 2.18 (2H, m),
2.45 (3H, s), 2.59 (2H, m), 3.32 (1H, t, J = 7Hz), 3.97
(2H, t, J = 7Hz), 4.20 (4H, q, J = 7Hz), 6.77 (2H, d, J = 8H
z), 7.06 (2H, d, J = 8Hz), 7.15 (2H, m), 7.25 (1H, m),
7.45 (1H, m)

(2) In the same manner as in Production Example 3- (6),
2-amino-2- [2- [4- [3- [dimethyl (2-
Methylphenyl) silyl] propoxy] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): 0.34 (6H, s), 0.92 (2H,
m), 1.28 (6H, t, J = 7Hz), 1.75 (2H, m), 2.02 (2H, br
s), 2.21 (2H, m), 2.45 (3H, s), 2.59 (2H, m), 3.86 (2
H, t, J = 7Hz), 4.22 (4H, q, J = 7Hz), 6.77 (2H, d, J = 8Hz),
7.07 (2H, d, J = 8Hz), 7.15 (2H, m), 7.25 (1H, m), 7.45
(1H, m)

Example 57 In the same manner as in Example 1- (1), 2-amino-2-
[2- [4- [3- [dimethyl (2-methylphenyl)
[Silyl] propoxy] phenyl] ethyl] -1,3-propanediol was obtained. NMR (DMSO-d ₆ , δ): 0.30 (6H, s), 0.88 (2
H, m), 1.44 (2H, m), 1.62 (4H, m), 2.50 (2H, m), 3.22
(4H, m), 3.84 (2H, t, J = 7Hz), 4.42 (2H, m), 6.75 (2H, d,
J = 8Hz), 7.04 (2H, d, J = 8Hz), 7.14 (2H, m), 7.25 (1H,
m), 7.40 (1H, m)

Production Example 58 (1) In the same manner as in Production Example 40- (4), 2- [2-
Diethyl [4- [3- (1-phenylsilacyclopent-1-yl) propoxy] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): 0.84 (4H, m), 0.99 (2H,
m), 1.25 (6H, t, J = 7Hz), 1.69 (4H, m), 1.83 (2H, m),
2.18 (2H, m), 2.59 (2H, dd, J = 7,7Hz), 3.32 (1H, t, J = 7H
z), 3.89 (2H, dd, J = 7,7Hz), 4.18 (4H, q, J = 7Hz), 6.77
(2H, d, J = 8Hz), 7.05 (2H, d, J = 8Hz), 7.33 (3H, m), 7.53
(2H, m)

(2) In the same manner as in Production Example 3- (6),
Diethyl 2-amino-2- [2- [4- [3- (1-phenylsilacyclopent-1-yl) propoxy] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): 0.85 (4H, m), 0.99 (2H,
m), 1.27 (6H, t, J = 7Hz), 1.70 (4H, m), 1.82 (2H, m),
2.02 (2H, br s), 2.22 (2H, m), 2.59 (2H, m), 3.90 (2H, m
t, J = 7Hz), 4.22 (4H, q, J = 7Hz), 6.79 (2H, d, J = 8Hz), 7.
09 (2H, d, J = 8Hz), 7.37 (3H, m), 7.53 (2H, m)

Example 58 In the same manner as in Example 1- (1), 2-amino-2-
[2- [4- [3- (1-phenylsilacyclopent-
1-yl) propoxy] phenyl] ethyl] -1,3-
Propanediol was obtained. NMR (DMSO-d ₆ , δ): 0.80 (4H, m), 0.97 (2
H, m), 1.45 (4H, m), 1.65 (4H, m), 1.73 (2H, m), 2.50
(2H, m), 3.22 (4H, m), 3.88 (2H, t, J = 7Hz), 4.43 (2H, m
m), 6.78 (2H, d, J = 8Hz), 7.06 (2H, d, J = 8Hz), 7.38 (3
H, m), 7.53 (2H, m)

Production Example 59 (1) In the same manner as in Production Example 40- (4), 2- [2-
Diethyl [4- [4- (dimethylpentylsilyl) butyloxy] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): -0.04 (6H, s), 0.52 (2H,
m), 0.59 (2H, m), 0.92 (3H, m), 1.31 (12H, m), 1.50
(2H, m), 1.82 (2H, m), 2.22 (2H, dt, J = 7,7Hz), 2.63 (2
H, dd, J = 7,7Hz), 3.37 (1H, t, J = 7Hz), 3.98 (2H, t, J = 7H)
z), 4.23 (4H, q, J = 7Hz), 6.85 (2H, d, J = 8Hz), 7.11 (2
(H, d, J = 8Hz)

(2) In the same manner as in Production Example 3- (6),
Diethyl 2-amino-2- [2- [4- [4- (dimethylpentylsilyl) butyloxy] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): -0.03 (6H, s), 0.55 (2H,
m), 0.62 (2H, m), 0.94 (3H, m), 1.33 (12H, m), 1.53
(2H, m), 1.84 (2H, m), 2.11 (2H, br s), 2.30 (2H, m),
2.64 (2H, m), 3.98 (2H, t, J = 7Hz), 4.27 (4H, q, J = 7Hz),
6.88 (2H, d, J = 8Hz), 7.15 (2H, d, J = 8Hz)

Example 59 In the same manner as in Example 1- (1), 2-amino-2-
[2- [4- [4- (Dimethylpentylsilyl) butyloxy] phenyl] ethyl] -1,3-propanediol was obtained. _{NMR (DMSO-d 6, δ} ): - 0.05 (6H, s), 0.47
(2H, m), 0.51 (2H, m), 0.85 (3H, m), 1.25 (8H, m), 1.4
2 (4H, m), 1.70 (2H, m), 2.50 (2H, m), 3.22 (4H, m),
3.90 (2H, t, J = 7Hz), 4.44 (2H, m), 6.78 (2H, d, J = 8Hz),
7.05 (2H, d, J = 8Hz)

Production Example 60 (1) In the same manner as in Production Example 40- (4), 2- [2-
[4- [3- (dimethylpentylsilyl) propoxy]
There was obtained diethyl [phenyl] ethyl] malonate. NMR (CDCl ₃ , δ): 0.00 (6H, d, J = 4 Hz), 0.53
(2H, m), 0.60 (2H, m), 0.90 (3H, m), 1.30 (12H, m), 1.
77 (2H, m), 2.19 (2H, m), 2.60 (2H, m), 3.33 (1H, t, J =
7Hz), 3.90 (2H, dd, J = 7,7Hz), 4.22 (4H, q, J = 7Hz), 6.8
1 (2H, d, J = 8Hz), 7.10 (2H, d, J = 8Hz)

(2) In the same manner as in Production Example 3- (6),
Diethyl 2-amino-2- [2- [4- [3- (dimethylpentylsilyl) propoxy] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): 0.01 (6H, s), 0.53 (2H,
m), 0.60 (2H, m), 0.90 (3H, m), 1.30 (12H, m), 1.78
(2H, m), 2.05 (2H, br s), 2.23 (2H, m), 2.60 (2H, m),
3.90 (2H, t, J = 7Hz), 4.23 (4H, q, J = 7Hz), 6.82 (2H, d, J
= 8Hz), 7.10 (2H, d, J = 8Hz)

Example 60 (1) In the same manner as in Example 1- (1), 2-amino-
2- [2- [4- [3- (Dimethylpentylsilyl) propoxy] phenyl] ethyl] -1,3-propanediol was obtained. NMR (DMSO-d ₆ , δ): -0.01 (6H, s), 0.52
(2H, m), 0.60 (2H, m), 0.87 (3H, m), 1.29 (8H, m), 1.4
8 (2H, m), 1.69 (2H, m), 2.50 (2H, m), 3.25 (2H, m),
3.88 (2H, t, J = 7Hz), 4.45 (2H, m), 6.80 (2H, d, J = 8Hz),
7.08 (2H, d, J = 8Hz)

(2) In the same manner as in Example 26- (2), 2-amino-2- [2- [4- [3- (dimethylpentylsilyl) propoxy] phenyl] ethyl] -1,
3-Propanediol hydrochloride was obtained. NMR (DMSO-d ₆ , δ): -0.02 (6H, s), 0.50
(2H, m), 0.58 (2H, m), 0.87 (3H, m), 1.28 (6H, m), 1.6
8 (2H, m), 1.76 (2H, m), 2.55 (2H, m), 3.51 (4H, H, d, J
= 5Hz), 3.88 (2H, t, J = 7Hz), 5.38 (2H, t, J = 5Hz), 6.83
(2H, d, J = 8Hz), 7.10 (2H, d, J = 8Hz), 7.86 (3H, br s)

Production Example 61 (1) In the same manner as in Production Example 40- (4), 2- [2-
Diethyl [4- [3- (3-chloro-4-methoxyphenyl) dimethylsilylpropoxy] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): 0.28 (6H, s), 0.82 (2H,
m), 1.26 (6H, t, J = 7Hz), 1.77 (2H, m), 2.18 (2H, m),
2.59 (2H, dd, J = 7,7Hz), 3.32 (1H, t, J = 7Hz), 3.87 (2H,
t, J = 7Hz), 3.90 (3H, s), 4.19 (4H, q, J = 7Hz), 6.77 (2
H, d, J = 8Hz), 6.92 (1H, d, J = 8Hz), 7.07 (2H, d, J = 8Hz),
7.35 (1H, d, J = 8Hz), 7.47 (1H, s)

(2) In the same manner as in Production Example 3- (6),
2-amino-2- [2- [4- [3- (3-chloro-4
-Dimethoxyphenyl) dimethylsilylpropoxy] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): 0.26 (6H, s), 0.82 (2H,
m), 1.28 (6H, t, J = 7Hz), 1.75 (2H, m), 2.01 (2H, br
s), 2.20 (2H, m), 2.55 (2H, m), 3.85 (2H, t, J = 7Hz), 3.
90 (3H, s), 4.21 (4H, q, J = 7Hz), 6.78 (2H, d, J = 8Hz),
6.90 (1H, d, J = 8Hz), 7.07 (2H, d, J = 8Hz), 7.33 (1H, d, J
= 8Hz), 7.45 (1H, s)

Example 61 In the same manner as in Example 1- (1), 2-amino-2-
[2- [4- [3- (3-Chloro-4-methoxyphenyl) dimethylsilylpropoxy] phenyl] ethyl]-
1,3-propanediol was obtained. NMR (DMSO-d ₆ , δ): 0.25 (6H, s), 0.80 (2
H, m), 1.27 (2H, br s), 1.44 (2H, m), 1.65 (2H, m), 2.5
0 (2H, m), 3.21 (4H, m), 3.33 (3H, s), 3.83 (2H, m),
3.84 (3H, s), 4.42 (2H, m), 6.75 (2H, d, J = 8Hz), 7.05
(2H, d, J = 8Hz), 7.13 (1H, d, J = 8Hz), 7.43 (1H, d, J = 8H
z), 7.48 (1H, s)

Production Example 62 (1) In the same manner as in Production Example 40- (4), 2- [2-
Diethyl [4- [4- (benzyldimethylsilyl) butyl] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): 0.04 (6H, s), 0.58 (2H,
m), 1.32 (6H, t, J = 7Hz), 1.40 (2H, m), 1.65 (2H, m),
2.12 (2H, s), 2.25 (2H, m), 2.61 (2H, m), 2.68 (2H, m
m), 3.39 (1H, t, J = 7Hz), 4.25 (4H, q, J = 7Hz), 7.03 (2
H, m), 7.11 (1H, m), 7.12 (4H, s), 7.25 (2H, m)

(2) In the same manner as in Production Example 3- (6),
Diethyl 2-amino-2- [2- [4- [4- (benzyldimethylsilyl) butyl] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): -0.05 (6H, s), 0.54 (2H,
m), 1.25 (6H, t, J = 7Hz), 1.30 (2H, m), 1.59 (2H, m), 2.
05 (4H, m), 2.25 (2H, m), 2.55 (2H, m), 2.63 (2H, m),
4.20 (4H, q, J = 7Hz), 6.95 (2H, m), 7.08 (5H, m), 7.18
(2H, m),

Example 62 In the same manner as in Example 1- (1), 2-amino-2-
[2- [4- [4- (Benzyldimethylsilyl) butyl] phenyl] ethyl] -1,3-propanediol was obtained. NMR (CDCl ₃ , δ): -0.10 (6H, s), 0.48 (2H,
m), 1.25 (4H, m), 1.47 (4H, m), 2.04 (2H, s), 2.50 (4
H, m), 3.22 (4H, m), 4.42 (2H, m), 6.95 (2H, d, J = 8Hz),
7.05 (5H, m), 7.18 (2H, m)

Production Example 63 (1) In the same manner as in Production Example 40- (4), 2- [2-
Diethyl [4- [4-dimethyl (3-trifluoromethylphenyl) silylbutyl] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): 0.28 (6H, s), 0.79 (2H,
m), 1.25 (6H, t, J = 7Hz), 1.37 (2H, m), 1.61 (2H, m),
2.20 (2H, m), 2.54 (2H, m), 2.62 (2H, m), 3.32 (1H, t,
J = 7Hz), 4.20 (4H, q, J = 7Hz), 7.05 (4H, s), 7.45 (1H,
m), 7.59 (1H, m), 7.67 (1H, m), 7.71 (1H, m)

(2) In the same manner as in Production Example 3- (6),
2-amino-2- [2- [4- [4-dimethyl (3-trifluoromethylphenyl) silylbutyl] phenyl]
[Ethyl] diethyl malonate was obtained.

Example 63 In the same manner as in Example 1- (1), 2-amino-2-
[2- [4- [4-dimethyl (3-trifluoromethylphenyl) silylbutyl] phenyl] ethyl] -1,3
-Propanediol was obtained. NMR (DMSO-d ₆ , δ): 0.25 (6H, s), 0.78 (2
H, m), 1.24 (2H, br s), 1.28 (2H, m), 1.44 (2H, m), 1.5
2 (2H, m), 2.50 (4H, m), 3.20 (4H, m), 4.43 (2H, m),
6.47 (2H, d, J = 8Hz), 7.03 (2H, d, J = 8Hz), 7.58 (1H, dd,
J = 8,8Hz), 7.73 (2H, m), 7.79 (1H, d, J = 8Hz)

Production Example 64 (1) In the same manner as in Production Example 40- (4), 2- [2-
Diethyl [4- [4-dimethyl (4-ethoxyphenyl) silylbutyl] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): 0.21 (6H, s), 0.73 (2H,
m), 1.27 (6H, t, J = 7Hz), 1.36 (2H, m), 1.42 (3H, t, J = 7
Hz), 1.60 (2H, m), 2.19 (2H, m), 2.53 (2H, m), 2.62
(2H, m), 3.33 (1H, t, J = 7Hz), 4.04 (2H, q, J = 7Hz), 4.19
(4H, q, J = 7Hz), 6.89 (2H, d, J = 8Hz), 7.07 (4H, s), 7.40
(2H, d, J = 8Hz)

(2) In the same manner as in Production Example 3- (6),
Diethyl 2-amino-2- [2- [4- [4-dimethyl (4-ethoxyphenyl) silylbutyl] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): 0.22 (6H, s), 0.75 (2H,
m), 1.29 (6H, t, J = 7Hz), 1.37 (2H, m), 1.44 (3H, t, J = 7
Hz), 1.60 (2H, m), 2.04 (2H, br s), 2.24 (2H, m), 2.54
(2H, m), 2.61 (2H, m), 4.05 (2H, q, J = 7Hz), 4.22 (4H, m
q, J = 7Hz), 6.90 (2H, d, J = 8Hz), 7.07 (4H, m), 7.42 (2
(H, d, J = 8Hz)

Example 64 In the same manner as in Example 1- (1), 2-amino-2-
[2- [4- [4-dimethyl (4-ethoxyphenyl)
[Silylbutyl] phenyl] ethyl] -1,3-propanediol was obtained. NMR (DMSO-d ₆ , δ): 0.20 (6H, s), 0.72 (2
H, m), 1.30 (4H, m), 1.34 (3H, t, J = 7Hz), 1.48 (2H, m),
1.55 (2H, m), 2.50 (2H, m), 3.23 (4H, m), 4.03 (2H, q,
J = 7Hz), 4.45 (2H, m), 6.91 (2H, d, J = 8Hz), 7.02 (2H,
d, J = 8Hz), 7.08 (2H, d, J = 8Hz), 7.39 (2H, d, J = 8Hz)

Production Example 65 (1) In the same manner as in Production Example 40- (4), 2- [2-
[4- [4- (ethylmethylphenylsilyl) butyl]
There was obtained diethyl [phenyl] ethyl] malonate. NMR (CDCl ₃ , δ): 0.22 (6H, s), 0.78 (4H,
m), 0.94 (3H, t, J = 7Hz), 1.26 (6H, t, J = 7Hz), 1.37 (2H,
m), 1.60 (2H, m), 2.20 (2H, m), 2.55 (2H, m), 2.62 (2
H, m), 3.33 (1H, t, J = 7Hz), 4.19 (4H, q, J = 7Hz), 7.05
(4H, s), 7.35 (3H, m), 7.49 (2H, m)

(2) In the same manner as in Production Example 3- (6),
Diethyl 2-amino-2- [2- [4- [4- (ethylmethylphenylsilyl) butyl] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): 0.22 (3H, s), 0.75 (2H,
m), 0.80 (2H, m), 0.95 (3H, m), 1.26 (6H, t, J = 7Hz),
1.36 (2H, m), 1.60 (2H, m), 2.02 (2H, br s), 2.23 (2H, m
m), 2.53 (2H, m), 2.60 (2H, m), 4.20 (4H, q, J = 7Hz),
7.04 (2H, d, J = 8Hz), 7.09 (2H, d, J = 8Hz), 7.34 (3H, m),
7.49 (2H, m)

Example 65 In the same manner as in Example 1- (1), 2-amino-2-
[2- [4- [4- (Ethylmethylphenylsilyl) butyl] phenyl] ethyl] -1,3-propanediol was obtained. NMR (CDCl ₃ , δ): 0.20 (3H, s), 0.70 (2H, q,
J = 7Hz), 0.77 (2H, m), 0.89 (3H, t, J = 7Hz), 1.25 (2H, b
rs), 1.30 (2H, m), 1.46 (2H, m), 1.55 (2H, m), 2.50
(4H, m), 3.23 (4H, m), 4.42 (2H, t, J = 5Hz), 7.00 (2H,
d, J = 8Hz), 7.05 (2H, d, J = 8Hz), 7.35 (3H, m), 7.47 (2
H, m)

Production Example 66 (1) In the same manner as in Production Example 40- (4), 2- [2-
There was obtained diethyl [4- [4- (1-butylsilacyclopent-1-yl) butyl] phenyl] ethyl] malonate. NMR (CDCl ₃ , δ): 0.45-0.65 (8H, m), 0.89
(3H, m), 1.25 (6H, t, J = 7Hz), 1.31 (2H, m), 1.38 (2H,
m), 1.52 (4H, m), 1.62 (2H, m), 2.20 (2H, dt, J = 7,7H
z), 2.58 (2H, dd, J = 7,7Hz), 2.63 (2H, dd, J = 7,7Hz), 3.
35 (1H, t, J = 7Hz), 4.20 (4H, q, J = 7Hz), 7.09 (4H, s)

(2) In the same manner as in Production Example 3- (6),
2-amino-2- [2- [4- [4- (1-butylsilacyclopent-1-yl) butyl] phenyl] ethyl]
Diethyl malonate was obtained. NMR (CDCl ₃ , δ): 0.45-0.65 (8H, m), 0.87
(3H, m), 1.26 (6H, t, J = 7Hz), 1.35 (6H, m), 1.50-1.70
(6H, m), 2.04 (2H, br s), 2.24 (2H, m), 2.55 (2H, m),
2.62 (2H, m), 4.21 (4H, q, J = 7Hz), 7.10 (4H, s)

Example 66 In the same manner as in Example 1- (1), 2-amino-2-
[2- [4- [4- (1-butylsilacyclopent-1)
-Yl) butyl] phenyl] ethyl] -1,3-propanediol was obtained. NMR (DMSO-d ₆ , δ): 0.48 (4H, m), 0.55 (2
H, m), 0.60 (2H, m), 0.85 (3H, m), 1.30 (8H, m), 1.50
(6H, m), 1.55 (2H, m), 2.53 (4H, m), 3.20 (4H, m), 4.4
3 (2H, m), 7.05 (4H, s)

Production Example 67 (1) In the same manner as in Production Example 40- (4), 2- [2-
Diethyl [4- [3- [dimethyl (3-methoxybenzyl) silyl] propylamino] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): 0.00 (6H, s), 0.57 (2H,
m), 1.27 (6H, t, J = 7Hz), 1.57 (4H, m), 2.10 (2H, s),
2.18 (2H, m), 2.55 (2H, dd, J = 7,7Hz), 3.05 (2H, dd, J =
7,7Hz), 3.34 (1H, t, J = 7Hz), 3.78 (3H, s), 4.20 (4H,
q, J = 7Hz), 6.5-6.65 (5H, m), 6.98 (2H, d, J = 8Hz), 7.13
(1H, dd, J = 8,8Hz)

(2) In the same manner as in Production Example 3- (6),
2-amino-2- [2- [4- [3- [dimethyl (3-
There was obtained diethyl methoxybenzyl) silyl] propylamino] phenyl] ethyl] malonate. NMR (CDCl ₃ , δ): 0.01 (6H, s), 0.58 (2H,
m), 1.27 (6H, t, J = 7Hz), 1.55 (4H, m), 2.09 (2H, s),
2.21 (2H, m), 2.53 (2H, m), 3.05 (2H, dd, J = 7,7Hz), 3.7
8 (3H, s), 4.23 (4H, q, J = 7Hz), 6.5-6.65 (5H, m), 7.00
(2H, d, J = 8Hz), 7.13 (1H, dd, J = 8,8Hz)

Example 67 In the same manner as in Example 1- (1), 2-amino-2-
[2- [4- [3- [dimethyl (3-methoxybenzyl) silyl] propylamino] phenyl] ethyl]-
1,3-propanediol was obtained. NMR (CDCl ₃ , δ): -0.05 (6H, s), 0.55 (2H,
m), 1.25 (2H, br s), 1.43 (2H, m), 1.51 (2H, m), 2.07
(2H, s), 2.40 (2H, m), 2.90 (2H, m), 3.20 (4H, m), 3.
70 (3H, s), 4.40 (2H, m), 5.28 (1H, m), 6.44 (2H, d, J =
8Hz), 6.60 (3H, m), 6.87 (2H, d, J = 8Hz), 7.10 (1H, dd,
(J = 8,8Hz)

Production Example 68 (1) 1,3-propanediol (9.86 g),
4-dihydro-2H-pyran (11.4 g) and p-
A mixture of pyridinium toluenesulfonate (326 mg) in dichloromethane (100 ml) was stirred at room temperature for 16 hours. The solvent was distilled off, and the residue was chromatographed on a silica gel column (hexane-ethyl acetate, 3: 2) to give 3-[(2-tetrahydropyranyl) oxy] propan-1-ol (11.2 g) as an oil. Obtained as a product. NMR (CDCl ₃ , δ): 1.45-1.9 (8H, m), 2.42 (5
H, t), 3.5-3.65 (2H, m), 3.75-4.0 (4H, m), 4.60 (1H, m)

(2) A mixture of 3-[(2-tetrahydropyranyl) oxy] propan-1-ol (11 g) and pyridine (14 ml) in dichloromethane (15 ml) was treated with p-toluenesulfonyl chloride (13.7).
g) and the mixture was stirred at room temperature for 18 hours. The mixture was concentrated, poured into ice water and extracted twice with ethyl acetate.
The combined organic solution was washed with brine, dried over magnesium sulfate and concentrated. The residue was purified by a silica gel column (hexane-ethyl acetate, 3: 1) to obtain 3-[(2-tetrahydropyranyl) oxy] propyl p-toluenesulfonate (16.5 g) as a colorless oil. NMR (CDCl ₃ , δ): 1.4-1.8 (6H, m), 1.92 (2
H, m), 2.44 (3H, s), 3.3-3.5 (2H, m), 3.76 (2H, m), 4.
17 (2H, m), 4.46 (1H, m), 7.35 (2H, d, J = 8Hz), 7.79 (2
(H, d, J = 8Hz)

(3) A Grignard reagent was prepared by a conventional method using magnesium (817 mg), allyl (chloromethyl) dimethylsilane (5 g) and tetrahydrofuran (50 ml). To this Grignard mixture was added dilithium tetrachlorocuprate (0.1 M in tetrahydrofuran, 6.7 ml) and 3-[(2-tetrahydropyranyl) oxy] propyl p-toluenesulfonate (7.55 g) in tetrahydrofuran (50 ml). ) Was added and the mixture was stirred at 40 ° C. for 24 hours. A saturated aqueous ammonium chloride solution was added to the mixture, and the mixture was extracted twice with ethyl acetate. The organic solution was washed with water, brine, dried over magnesium sulfate and concentrated. The residue was chromatographed on a silica gel column [3% ethyl acetate (in hexane)] to give 2- [4- (allyldimethylsilyl) butoxy] tetrahydropyran (2.82 g) as an oil. NMR (CDCl ₃ , δ): -0.02 (6H, s), 0.56 (2H,
m), 1.35-1.9 (12H, m), 3.38 (1H, m), 3.50 (1H, m), 3.
76 (1H, m), 3.87 (1H, m), 4.58 (1H, m), 4.8-4.9 (2H,
m), 5.78 (1H, m)

(4) A mixture of 2- [4- (allyldimethylsilyl) butoxy] tetrahydropyran (2.81 g) and pyridinium p-toluenesulfonate (55 mg) in methanol (30 ml) was refluxed for 1.5 hours. Stirred for hours. The mixture was concentrated and the residue was purified on a silica gel column (hexane-ethyl acetate, 7: 1) to give 4- (allyldimethylsilyl) butan-1-ol (1.16).
g) was obtained as an oil. NMR (DMSO-d ₆ , δ): -0.01 (6H, s), 0.51
(2H, m), 1.25-1.55 (6H, m), 3.40 (2H, m), 4.32 (1H, t,
J = 5Hz), 4.8-4.9 (2H, m), 5.79 (1H, m)

(5) 4- (allyldimethylsilyl) butan-1-ol (1.15 g) and 2- [2- (4-
[Hydroxyphenyl) ethyl] malonate diethyl (2.
06g) in dichloromethane (30 ml).
Treated with triphenylphosphine (1.93 g) and diethyl azodicarboxylate (1.16 ml) at ° C. The mixture was stirred at 0 ° C. for 2 hours and concentrated. The residue was chromatographed on a silica gel column [8% ethyl acetate (in hexane)] to give diethyl 2- [2- [4- [4- (allyldimethylsilyl) butoxy] phenyl] ethyl] malonate (1.14 g). Was obtained as an oil. NMR (CDCl ₃ , δ): 0.00 (6H, s), 0.58 (2H,
m), 1.28 (6H, t, J = 7Hz), 1.4-1.55 (4H, m), 1.79 (2H,
m), 2.18 (2H, q, J = 7Hz), 2.59 (2H, t, J = 7Hz), 3.32 (1H,
(t, J = 7Hz), 3.93 (2H, t, J = 7Hz), 4.20 (4H, q, J = 7Hz), 4.
8-4.9 (2H, m), 5.78 (1H, m), 6.82 (2H, d, J = 8Hz), 7.09
(2H, d, J = 8Hz)

(6) In the same manner as in Production Example 3- (6),
Diethyl 2-amino-2- [2- [4- [4- (allyldimethylsilyl) butoxy] phenyl] ethyl] malonate was obtained. NMR (DMSO-d ₆ , δ): -0.02 (6H, s), 0.56
(2H, m), 1.18 (6H, t, J = 7Hz), 1.4-1.55 (4H, m), 1.71
(2H, m), 2.03 (2H, m), 2.31 (2H, br s), 2.48 (2H, m),
3.91 (2H, t, J = 7Hz), 4.13 (4H, q, J = 7Hz), 4.8-4.9 (2H,
m), 5.77 (1H, m), 6.82 (2H, d, J = 8Hz), 7.07 (2H, d, J = 8
Hz)

Example 68 In the same manner as in Example 1- (1), 2-amino-2-
[2- [4- [4- (Allyldimethylsilyl) butoxy] phenyl] ethyl] -1,3-propanediol was obtained. NMR (DMSO-d ₆ , δ): -0.02 (6H, s), 0.57
(2H, m), 1.4-1.8 (10H, m), 2.49 (2H, m), 3.25 (4H, m),
3.91 (2H, t, J = 7Hz), 4.48 (2H, br s), 4.8-4.9 (2H,
m), 5.77 (1H, m), 6.80 (2H, d, J = 8Hz), 7.07 (2H, d, J = 8
Hz)

Production Example 69 (1) A mixture of 1,7-heptanediol (12.5 g) and triethylamine (31.6 ml) in dichloromethane (150 ml) was treated at 0 ° C. with methanesulfonyl.
Treated with chloride (16.1 ml). Reaction mixture
Stirred at C for 1 hour and concentrated. Water was added to the residue and extracted twice with ethyl acetate. The organic solution was washed with 0.5N hydrochloric acid and a saturated aqueous solution of sodium hydrogen carbonate, and dried over magnesium sulfate. The solvent was distilled off, and the obtained solid was washed with isopropyl ether to obtain heptamethylenedimethanesulfonate (19.9 g) as a solid. NMR (CDCl ₃ , δ): 1.3-1.5 (6H, m), 1.77 (4
H, m), 3.00 (6H, s), 4.22 (4H, t, J = 7Hz)

(2) Heptamethylene dimethanesulfonate (14.4 g) in tetrahydrofuran (150 m
l) was mixed with dilithium tetrachlorocuprate (0.1
(M tetrahydrofuran solution, 5 ml) and trimethylsilylmagnesium chloride (1 M diethyl ether solution, 50 ml), and the mixture was stirred at room temperature for 44 hours. To the mixture was added a saturated aqueous ammonium chloride solution,
Extracted twice with ethyl acetate. The organic solution was washed with water, brine, dried over magnesium sulfate and concentrated. The residue was chromatographed on a silica gel column [15% ethyl acetate (in hexane)] to give 8- (trimethylsilyl).
Octyl methanesulfonate (5.41 g) was obtained as an oil. NMR (CDCl ₃ , δ): -0.03 (9H, s), 0.47 (2H,
m), 1.2-1.45 (10H, m), 1.75 (2H, m), 3.00 (3H, s), 4.
22 (2H, t, J = 7Hz)

(3) In the same manner as in Production Example 1- (6),
8- (Trimethylsilyl) octyl iodide was obtained. NMR (CDCl ₃ , δ): -0.03 (9H, s), 0.47 (2H,
m), 1.2-1.45 (10H, m), 1.83 (2H, m), 3.19 (2H, t, J = 7H
z)

(4) In the same manner as in Production Example 68- (3), 2- [2- [4- [8- (trimethylsilyl) octyl] phenyl] ethoxy] tetrahydropyran was obtained. NMR (CDCl ₃ , δ): -0.03 (9H, s), 0.47 (2H,
m), 1.2-1.4 (10H, m), 1.45-1.9 (8H, m), 2.57 (2H, t, J
= 7Hz), 2.88 (2H, t, J = 7Hz), 3.46 (1H, m), 3.61 (1H,
m), 3.77 (1H, m), 3.94 (1H, m), 4.59 (1H, m), 7.12 (4
H, m)

(5) In the same manner as in Production Example 68- (4), 2- [4- [8- (trimethylsilyl) octyl]
[Phenyl] ethanol was obtained. NMR (DMSO-d ₆ , δ): -0.04 (9H, s), 0.46
(2H, m), 1.2-1.35 (10H, m), 1.53 (2H, m), 2.50 (2H, t,
J = 7Hz), 2.66 (2H, t, J = 7Hz), 3.56 (2H, m), 4.59 (1H, t,
J = 5Hz), 7.07 (4H, m)

(6) In the same manner as in Production Example 19- (4), 2- [4- [8- (trimethylsilyl) octyl]
[Phenyl] ethyl iodide was obtained. NMR (CDCl ₃ , δ): -0.04 (9H, s), 0.46 (2H,
m), 1.2-1.4 (10H, m), 1.59 (2H, m), 2.57 (2H, t, J = 7H
z), 3.15 (2H, t, J = 7Hz), 3.34 (2H, t, J = 7Hz), 7.11 (4H,
m)

(7) In the same manner as in Production Example 74- (3), diethyl 2- [2- [4- [8- (trimethylsilyl) octyl] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): -0.03 (9H, s), 0.47 (2H,
m), 1.1-1.2 (10H, m), 1.59 (2H, m), 2.21 (2H, q, J = 7H
z), 2.5-2.7 (4H, m), 3.35 (1H, t, J = 7Hz), 4.19 (4H, q,
J = 7Hz), 7.09 (4H, m)

(8) In the same manner as in Production Example 3- (6),
Diethyl 2-amino-2- [2- [4- [8- (trimethylsilyl) octyl] phenyl] ethyl] malonate was obtained. NMR (DMSO-d ₆ , δ): -0.04 (6H, s), 0.46
(2H, m), 1.17 (6H, t, J = 7Hz), 1.2-1.3 (10H, m), 1.53
(2H, m), 2.05 (2H, m), 2.33 (2H, s), 2.52 (4H, m), 4.12
(4H, q, J = 7Hz), 7.07 (4H, m)

Example 69 In the same manner as in Example 1- (1), 2-amino-2-
[2- [4- [8- (Trimethylsilyl) octyl] phenyl] ethyl] -1,3-propanediol was obtained. NMR (DMSO-d ₆ , δ): 0.00 (9H, s), 0.49 (2
H, m), 1.2-1.35 (10H, m), 1.4-1.7 (4H, m), 2.5-2.6 (4
H, m), 3.27 (4H, m), 4.50 (2H, br s), 7.10 (4H, m)

Production Example 70 (1) In the same manner as in Production Example 40- (4), 2- [2-
Diethyl [4- [3-[(2-methoxyphenyl) dimethylsilyl] propoxy] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): 0.28 (6H, s), 0.89 (2H,
m), 1.27 (6H, t, J = 7Hz), 1.77 (2H, m), 2.18 (2H, m),
2.58 (2H, t, J = 7Hz), 3.31 (1H, t, J = 7Hz), 3.79 (3H, s),
3.85 (2H, t, J = 7Hz), 4.19 (4H, q, J = 7Hz), 6.7-6.85 (3
H, m), 6.93 (1H, t, J = 8Hz), 7.06 (2H, d, J = 8Hz), 7.3-7.
4 (2H, m)

(2) In the same manner as in Production Example 3- (6),
Diethyl 2-amino-2- [2- [4- [3-[(2-methoxyphenyl) dimethylsilyl] propoxy] phenyl] ethyl] malonate was obtained. NMR (DMSO-d ₆ , δ): 0.23 (6H, s), 0.83 (2
H, m), 1.18 (6H, t, J = 7Hz), 1.65 (2H, m), 2.01 (2H, m),
2.31 (2H, br s), 2.47 (2H, m), 3.76 (3H, s), 3.84 (2
H, t, J = 7Hz), 4.11 (4H, q, J = 7Hz), 6.78 (2H, d, J = 8Hz),
6.93 (2H, m), 7.05 (2H, d, J = 8Hz), 7.3-7.4 (2H, m)

Example 70 In the same manner as in Example 1- (1), 2-amino-2-
[2- [4- [3-[(2-methoxyphenyl) dimethylsilyl] propoxy] phenyl] ethyl] -1,3-
Propanediol was obtained. NMR (DMSO-d ₆ , δ): 0.23 (6H, s), 0.83 (2
H, m), 1.30 (2H, br s), 1.45 (2H, m), 1.65 (2H, m), 2.4
9 (2H, m), 3.22 (4H, m), 3.76 (3H, s), 3.82 (2H, t, J = 7
Hz), 4.42 (2H, m), 6.75 (2H, d, J = 8Hz), 6.93 (2H, m),
7.05 (2H, d, J = 8Hz), 7.3-7.4 (2H, m)

Production Example 71 (1) In the same manner as in Production Example 40- (4), 2- [2-
Diethyl [4- [3-[(2-chlorophenyl) dimethylsilyl] propoxy] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): 0.38 (6H, s), 1.02 (2H,
m), 1.27 (6H, t, J = 7Hz), 1.78 (2H, m), 2.18 (2H, m),
2.59 (2H, t, J = 7Hz), 3.32 (1H, t, J = 7Hz), 3.88 (2H, t, J
= 7Hz), 4.19 (4H, q, J = 7Hz), 6.77 (2H, d, J = 8Hz), 7.06
(2H, d, J = 8Hz), 7.2-7.35 (3H, m), 7.44 (1H, m)

(2) In the same manner as in Production Example 3- (6),
Diethyl 2-amino-2- [2- [4- [3-[(2-chlorophenyl) dimethylsilyl] propoxy] phenyl] ethyl] malonate was obtained. NMR (DMSO-d ₆ , δ): 0.38 (6H, s), 1.00 (2
H, m), 1.19 (6H, t, J = 7Hz), 1.58 (2H, m), 2.05 (2H, m),
2.33 (2H, s), 2.49 (2H, m), 3.88 (2H, t, J = 7Hz), 4.15
(4H, q, J = 7Hz), 6.80 (2H, d, J = 8Hz), 7.07 (2H, d, J = 8H
z), 7.3-7.55 (4H, m)

Example 71 In the same manner as in Example 1- (1), 2-amino-2-
[2- [4- [3-[(2-Chlorophenyl) dimethylsilyl] propoxy] phenyl] ethyl] -1,3-propanediol was obtained. NMR (DMSO-d ₆ , δ): 0.23 (6H, s), 0.83 (2
H, m), 1.30 (2H, br s), 1.45 (2H, m), 1.65 (2H, m), 2.4
9 (2H, m), 3.22 (4H, m), 3.76 (3H, s), 3.82 (2H, t, J = 7
Hz), 4.42 (2H, m), 6.75 (2H, d, J = 8Hz), 6.93 (2H, m),
7.05 (2H, d, J = 8Hz), 7.3-7.4 (2H, m)

Production Example 72 (1) In the same manner as in Production Example 40- (4), 2- [2-
Diethyl [4- [4-[(2-methoxyphenyl) dimethylsilyl] butyl] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): 0.23 (6H, s), 0.81 (2H,
m), 1.27 (6H, t, J = 7Hz), 1.36 (2H, m), 1.59 (2H, m),
2.19 (2H, m), 2.5-2.7 (4H, m), 3.32 (1H, t, J = 7Hz), 3.7
8 (3H, s), 4.18 (4H, q, J = 7Hz), 6.81 (1H, d, J = 8Hz), 6.
93 (1H, t, J = 8Hz), 7.0-7.1 (4H, m), 7.3-7.4 (2H, m)

(2) In the same manner as in Production Example 3- (6),
Diethyl 2-amino-2- [2- [4- [4-[(2-methoxyphenyl) dimethylsilyl] butyl] phenyl] ethyl] malonate was obtained. NMR (DMSO-d ₆ , δ): 0.20 (6H, s), 0.78 (2
H, m), 1.18 (6H, t, J = 7Hz), 1.28 (2H, m), 1.52 (2H, m),
2.02 (2H, m), 2.31 (2H, s), 2.49 (4H, m), 3.73 (3H,
s), 4.11 (4H, q, J = 7Hz), 6.92 (2H, m), 7.04 (4H, m),
7.28 (1H, d, J = 7Hz), 7.35 (1H, t, J = 7Hz)

Example 72 In the same manner as in Example 1- (1), 2-amino-2-
[2- [4- [4-[(2-methoxyphenyl) dimethylsilyl] butyl] phenyl] ethyl] -1,3-propanediol was obtained. NMR (DMSO-d ₆ , δ): 0.20 (6H, s), 0.78 (2
H, m), 1.27 (4H, m), 1.50 (4H, m), 1.45-2.55 (4H, m),
3.22 (4H, m), 4.43 (2H, t, J = 5Hz), 6.92 (2H, m), 7.02
(2H, m), 7.28 (1H, d, J = 8Hz), 7.36 (1H, t, J = 8Hz)

Production Example 73 (1) In the same manner as in Production Example 40- (4), 2- [2-
Diethyl [4- [4- (1-benzylsilacyclopent-1-yl) butoxy] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): 0.45-0.7 (6H, m), 1.27 (6
(H, t, J = 7Hz), 1.3-1.55 (6H, m), 1.77 (2H, m), 2.18 (2
H, m), 2.59 (2H, t, J = 7Hz), 3.32 (1H, t, J = 7Hz), 3.90
(2H, t, J = 7Hz), 4.19 (4H, q, J = 7Hz), 6.81 (2H, d, J = 8H
z), 7.0-7.25 (7H, m)

(2) In the same manner as in Production Example 3- (6),
Diethyl 2-amino-2- [2- [4- [4- (1-benzylsilacyclopent-1-yl) butoxy] phenyl] ethyl] malonate was obtained. NMR (DMSO-d ₆ , δ): 0.4-0.7 (6H, m), 1.18
(6H, t, J = 7Hz), 1.2-1.5 (6H, m), 1.69 (2H, m), 2.02 (2
H, m), 2.31 (2H, s), 2.48 (2H, m), 3.90 (2H, t, J = 7Hz),
4.11 (4H, q, J = 7Hz), 6.82 (2H, d, J = 8Hz), 7.0-7.2 (7
H, m)

Example 73 In the same manner as in Example 1- (1) and Example 26- (2), 2-amino-2- [2- [4- [4- (1-benzylsilacyclopent- 1-yl) butoxy] phenyl] ethyl] -1,3-propanediol hydrochloride was obtained. NMR (DMSO-d ₆ , δ): 0.4-0.7 (6H, m), 1.2-
1.5 (6H, m), 1.6-1.8 (4H, m), 2.52 (2H, m), 3.51 (4H, m
m), 3.90 (2H, t, J = 7Hz), 5.38 (2H, t, J = 5Hz), 6.83 (2
(H, d, J = 8Hz), 7.0-7.2 (7H, m), 7.88 (3H, br s)

Production Example 74 (1) 2- (4-Nitrophenyl) ethanol (100
g) and triethylamine (167 ml) in chloroform (800 ml).
Chloride (70 ml) was added. The mixture was stirred at room temperature for 1 hour and concentrated under reduced pressure. Water was added to the residue and extracted twice with ethyl acetate. The organic solution was washed with 0.5N hydrochloric acid and a saturated aqueous solution of sodium hydrogen carbonate, and dried over magnesium sulfate. The solvent was distilled off, and the obtained solid was collected and washed with isopropyl ether to obtain 2- (4-nitrophenyl) ethyl methanesulfonate (124 g) as a pale yellow solid. NMR (CDCl ₃ , δ): 2.95 (3H, s), 3.19 (2H, t,
J = 7Hz), 4.48 (2H, t, J = 7Hz), 7.42 (2H, d, J = 8Hz), 8.20
(2H, d, J = 8Hz)

(2) A mixture of 2- (4-nitrophenyl) ethyl methanesulfonate (124 g) and sodium iodide (98.5 g) in acetone (1000 ml) was refluxed for 6 hours. The solvent was distilled off, and ethyl acetate was added to the residue. The organic solution was washed with water, brine, and dried over magnesium sulfate. The solvent was distilled off, and the obtained solid was washed with isopropyl ether to obtain 2- (4-nitrophenyl) ethyl iodide (114 g) as a solid. NMR (CDCl ₃ , δ): 3.25-3.45 (4H, m), 7.38
(2H, d, J = 8Hz), 8.20 (2H, d, J = 8Hz)

(3) To a suspension of sodium hydride (19.7 g, 60% in oil) in tetrahydrofuran (200 ml) was added diethyl malonate (93 ml) in tetrahydrofuran (200 ml). When the mixture became clear, 2- (4-) in tetrahydrofuran (500 ml) was used.
(Nitrophenyl) ethyl iodide (113.5 g) was added, and the mixture was stirred at room temperature for 4 hours. The mixture was concentrated, ice water was added to the residue, and the mixture was extracted twice with ethyl acetate. The organic solution was washed with water, brine, dried over magnesium sulfate, and concentrated to give diethyl 2- [2- (4-nitrophenyl) ethyl] malonate (100.9 g) as an oil. NMR (CDCl ₃ , δ): 1.28 (6H, t, J = 7Hz), 2.24
(2H, q, J = 7Hz), 2.78 (2H, t, J = 7Hz), 3.33 (2H, t, J = 7H
z), 4.21 (4H, q, J = 7Hz), 7.36 (2H, d, J = 8Hz), 8.17 (2H,
d, J = 8Hz)

(4) 2- [2- (4-nitrophenyl)
Ethyl] diethyl malonate (45.0 g) and ammonium chloride (46.7 g) in ethanol (390 ml)
And iron powder (24.4) in a mixture in water and 130 ml of water.
g) was added. The mixture was stirred at 90 ° C. for 1 hour, and the insolubles were filtered off while hot. The filtrate was concentrated, and ethyl acetate was added to the residue. The mixture was washed with a saturated aqueous sodium hydrogen carbonate solution and brine, dried over magnesium sulfate, and concentrated to give diethyl 2- [2- (4-aminophenyl) ethyl] malonate (38.6 g) as an oil. . _{NMR (DMSO-d 6, δ} ): 1.18 (6H, t, J = 7Hz),
1.96 (2H, q, J = 7Hz), 2.38 (2H, t, J = 7Hz), 3.34 (1H, t, J =
7Hz), 4.11 (4H, q, J = 7Hz), 4.85 (2H, s), 6.48 (2H, d, J
= 8Hz), 6.80 (2H, d, J = 8Hz)

(5) 2- [2- (4-aminophenyl)
A mixture of diethyl [ethyl] malonate (4.12 g), allyl bromide (1.4 ml) and potassium carbonate (2.45 g) in N, N-dimethylformamide (40 ml) was stirred at 40 ° C. for 1 hour. The mixture was poured into water and extracted twice with ethyl acetate. The organic solution was washed with a saturated aqueous solution of sodium bicarbonate, brine, dried over magnesium sulfate and concentrated. The residue was chromatographed on a silica gel column (hexane-ethyl acetate, 7: 1) to give 2-
Diethyl [2- (4-allylaminophenyl) ethyl] malonate (1.84 g) was obtained as an oil. _{NMR (DMSO-d 6, δ} ): 1.18 (6H, t, J = 7Hz),
1.96 (2H, q, J = 7Hz), 2.40 (2H, t, J = 7Hz), 3.34 (1H, t, J =
7Hz), 3.63 (2H, m), 4.11 (4H, q, J = 7Hz), 5.08 (1H, d, J
= 9Hz), 5.21 (1H, d, J = 16Hz), 5.63 (1H, t, J = 6Hz), 5.88
(1H, m), 6.49 (2H, d, J = 8Hz), 6.87 (2H, d, J = 8Hz)

(6) In the same manner as in Production Example 40- (4), diethyl 2- [2- [4- [3- (dimethylphenylsilyl) propyl] aminophenyl] ethyl] malonate was obtained. NMR (DMSO-d ₆ , δ): 0.24 (6H, s), 0.79 (2
H, m), 1.18 (6H, t, J = 7Hz), 1.50 (2H, m), 1.97 (2H, q, J
= 7Hz), 2.39 (2H, t, J = 7Hz), 2.92 (2H, m), 3.34 (1H, t, J
= 7Hz), 4.11 (4H, q, J = 7Hz), 5.39 (1H, t, J = 6Hz), 6.42
(2H, d, J = 8Hz), 6.84 (2H, d, J = 8Hz), 7.36 (3H, m), 7.50
(2H, m)

(7) In the same manner as in Production Example 3- (6),
Diethyl 2-amino-2- [2- [4- [3- (dimethylphenylsilyl) propyl] aminophenyl] ethyl] malonate was obtained. NMR (DMSO-d ₆ , δ): 0.24 (6H, s), 0.79 (2
H, m), 1.18 (6H, t, J = 7Hz), 1.50 (1H, m), 1.98 (2H, m),
2.28 (2H, s), 2.37 (2H, m), 2.92 (2H, m), 4.11 (4H, t,
J = 7Hz), 5.35 (1H, t, J = 6Hz), 6.42 (2H, d, J = 8Hz), 6.84
(2H, d, J = 8Hz), 7.37 (3H, m), 7.50 (2H, m)

Example 74 In the same manner as in Example 1- (1), 2-amino-2-
[2- [4- [3- (Dimethylphenylsilyl) propyl] aminophenyl] ethyl] -1,3-propanediol was obtained. NMR (DMSO-d ₆ , δ): 0.25 (6H, s), 0.79 (2
H, m), 1.4-1.55 (4H, m), 1.93 (2H, br s), 2.40 (2H, m),
2.91 (2H, m), 3.22 (4H, m), 4.48 (2H, br s), 5.28 (1
H, t, J = 6Hz), 6.41 (2H, d, J = 8Hz), 6.85 (2H, d, J = 8Hz),
7.36 (3H, m), 7.50 (2H, m)

Production Example 75 (1) Diethyl 2- [2- [4- [3- (dimethylphenylsilyl) propyl] aminophenyl] ethyl] malonate (3.3 g), iodomethane (4.5 ml) and potassium carbonate (1.1 g) was stirred at room temperature for 3.5 hours. The insolubles were removed by filtration, and the filtrate was concentrated. The residue was chromatographed on a silica gel column (hexane-ethyl acetate, 7: 1) to give 2- [2- [4- [N- [3
-(Dimethylphenylsilyl) propyl] -N-methylamino] phenyl] ethyl] diethyl malonate (1.5
8g) was obtained as an oil. NMR (DMSO-d ₆ , δ): 0.22 (6H, s), 0.70 (2
H, m), 1.18 (6H, t, J = 7Hz), 1.46 (2H, m), 1.98 (2H, q, J
= 7Hz), 2.42 (2H, t, J = 7Hz), 2.79 (3H, s), 3.21 (1H, t, J
= 7Hz), 3.36 (1H, t, J = 7Hz), 4.11 (4H, q, J = 7Hz), 6.53
(2H, d, J = 8Hz), 6.92 (2H, d, J = 8Hz), 7.36 (3H, m), 7.49
(2H, m)

(2) In the same manner as in Production Example 3- (6),
Diethyl 2-amino-2- [2- [4- [N- [3- (dimethylphenylsilyl) propyl] -N-methylamino] phenyl] ethyl] malonate was obtained. NMR (DMSO-d ₆ , δ): 0.24 (6H, s), 0.71 (2
H, m), 1.18 (6H, t, J = 7Hz), 1.47 (2H, m), 2.00 (2H, m),
2.29 (2H, s), 2.41 (2H, m), 2.80 (3H, s), 3.22 (2H, t,
J = 7Hz), 4.12 (4H, q, J = 7Hz), 6.54 (2H, d, J = 8Hz), 6.93
(2H, d, J = 8Hz), 7.37 (3H, m), 7.50 (2H, m)

Example 75 In the same manner as in Example 1- (1), 2-amino-2-
[2- [4- [N- [3- (dimethylphenylsilyl)
Propyl] -N-methylamino] phenyl] ethyl]-
1,3-propanediol was obtained. NMR (DMSO-d ₆ , δ): 0.23 (6H, s), 0.69 (2
H, m), 1.23 (2H, s), 1.9-2.0 (4H, m), 2.42 (2H, m), 2.
78 (3H, s), 3.15-3.3 (6H, m), 4.40 (2H, t, J = 5Hz), 6.5
2 (2H, d, J = 8Hz), 6.93 (2H, d, J = 8Hz), 7.37 (3H, m), 7.
49 (2H, m)

Production Example 76 (1) In the same manner as in Production Example 40- (4), 2- [2-
Diethyl [4- [3- [dimethyl (1-naphthyl) silyl] propyl] aminophenyl] ethyl] malonate was obtained. NMR (DMSO-d ₆ , δ): 0.43 (6H, s), 1.02 (2
H, m), 1.18 (6H, t, J = 7Hz), 1.51 (2H, m), 1.95 (2H, m),
2.38 (2H, m), 2.91 (2H, m), 3.33 (1H, m), 4.11 (4H, q,
J = 7Hz), 5.38 (1H, m), 6.38 (2H, d, J = 8Hz), 6.81 (2H,
d, J = 8Hz), 7.45-7.6 (3H, m), 7.68 (1H, d, J = 7Hz), 7.94
(2H, d, J = 8Hz), 8.08 (1H, d, J = 8Hz)

(2) In the same manner as in Production Example 3- (6),
2-amino-2- [2- [4- [3- [dimethyl (1-
Naphthyl) silyl] propyl] aminophenyl] ethyl] diethyl malonate was obtained. NMR (DMSO-d ₆ , δ): 0.43 (6H, s), 1.01 (2
H, m), 1.18 (6H, t, J = 7Hz), 1.50 (2H, m), 1.97 (2H, m),
2.27 (2H, s), 2.35 (2H, m), 2.90 (2H, m), 4.11 (4H, q,
J = 7Hz), 5.32 (1H, t, J = 6Hz), 6.38 (2H, d, J = 8Hz), 6.81
(2H, d, J = 8Hz), 7.45-7.6 (3H, m), 7.68 (1H, d, J = 7Hz),
7.94 (2H, d, J = 8Hz), 8.08 (1H, d, J = 8Hz)

Example 76 In the same manner as in Example 1- (1), 2-amino-2-
[2- [4- [3- [Dimethyl (1-naphthyl) silyl] propyl] aminophenyl] ethyl] -1,3-propanediol was obtained. NMR (DMSO-d ₆ , δ): 0.43 (6H, s), 1.02 (2
H, m), 1.25-1.6 (6H, m), 2.39 (2H, m), 2.90 (2H, m), 3.
21 (4H, m), 4.40 (2H, s), 5.23 (1H, t, J = 6Hz), 6.37 (2
(H, d, J = 8Hz), 6.82 (2H, d, J = 8Hz), 7.45-7.6 (3H, m), 7.
68 (1H, d, J = 7Hz), 7.95 (2H, d, J = 8Hz), 8.08 (1H, d, J = 8
Hz)

Production Example 77 (1) In the same manner as in Production Example 40- (4), 2- [2-
Diethyl [4- [3- (1-butylsilacyclopent-1-yl) propyl] aminophenyl] ethyl] malonate was obtained. _{NMR (DMSO-d 6, δ} ): 1.18 (6H, t, J = 7Hz),
1.29 (6H, m), 1.45-1.7 (8H, m), 1.86 (3H, t, J = 7Hz),
1.97 (2H, m), 2.39 (2H, t, J = 7Hz), 2.93 (2H, m), 3.35
(1H, t, J = 7Hz), 4.11 (4H, q, J = 7Hz), 5.40 (1H, t, J = 6H)
z), 6.47 (2H, d, J = 8Hz), 6.86 (2H, d, J = 8Hz)

(2) In the same manner as in Production Example 3- (6),
2-amino-2- [2- [4- [3- (1-butylsilacyclopent-1-yl) propyl] aminophenyl]
[Ethyl] diethyl malonate was obtained.

Example 77 In the same manner as in Example 1- (1), 2-amino-2-
[2- [4- [3- (1-butylsilacyclopent-1)
-Yl) propyl] aminophenyl] ethyl] -1,3
-Propanediol was obtained. NMR (DMSO-d ₆ , δ): 0.85 (3H, t, J = 7Hz),
1.2-1.6 (12H, m), 1.4-1.7 (8H, m), 1.90 (2H, br s),
2.40 (2H, m), 2.92 (2H, m), 3.23 (4H, m), 4.46 (2H, br
s), 5.29 (1H, t, J = 6Hz), 6.44 (2H, d, J = 8Hz), 6.88 (2
(H, d, J = 8Hz)

Production Example 78 (1) Diethyl 2- [2- (4-aminophenyl) ethyl] malonate (25.1 g), 4-bromo-1-butene (18.2 ml), potassium carbonate (13.7 g) ) And potassium iodide (14.9 g) in 1,4-dioxane (80 ml) were refluxed for 4 hours. The insolubles were removed by filtration, and the filtrate was concentrated. Water was added to the residue and extracted twice with ethyl acetate. The organic solution was washed with a saturated aqueous solution of sodium bicarbonate, brine, dried over magnesium sulfate and concentrated. The residue was chromatographed on a silica gel column (hexane-ethyl acetate, 7: 1) to give 2- [2-
Diethyl [4- (3-butenyl) aminophenyl] ethyl] malonate (10.2 g) was obtained as an oil. _{NMR (DMSO-d 6, δ} ): 1.18 (6H, t, J = 7Hz),
1.97 (2H, m), 2.28 (2H, m), 2.40 (2H, t, J = 7Hz), 3.02
(2H, m), 3.35 (1H, t, J = 7Hz), 4.11 (4H, q, J = 7Hz), 5.0-
5.15 (2H, m), 5.38 (1H, t, J = 6Hz), 5.87 (1H, m), 6.49
(2H, d, J = 8Hz), 6.88 (2H, d, J = 8Hz)

(2) In the same manner as in Production Example 40- (4), diethyl 2- [2- [4- [4- (dimethylphenylsilyl) butyl] aminophenyl] ethyl] malonate was obtained. NMR (DMSO-d ₆ , δ): 0.23 (6H, s), 0.75 (2
H, m), 1.18 (6H, t, J = 7Hz), 1.38 (2H, m), 1.53 (2H, m),
1.97 (2H, m), 2.40 (2H, t, J = 7Hz), 2.92 (2H, m), 3.35
(1H, t, J = 7Hz), 4.11 (4H, q, J = 7Hz), 5.32 (1H, t, J = 6H
z), 6.45 (2H, d, J = 8Hz), 6.86 (2H, d, J = 8Hz), 7.35 (3
H, m), 7.50 (2H, m)

(3) In the same manner as in Production Example 3- (6),
Diethyl 2-amino-2- [2- [4- [4- (dimethylphenylsilyl) butyl] aminophenyl] ethyl] malonate was obtained. NMR (DMSO-d ₆ , δ): 0.23 (6H, s), 0.74 (2
H, m), 1.18 (6H, t, J = 7Hz), 1.37 (2H, m), 1.53 (2H, m),
1.98 (2H, m), 2.27 (2H, s), 2.37 (2H, m), 2.92 (2H, m
m), 4.11 (4H, q, J = 7Hz), 5.28 (1H, t, J = 6Hz), 6.44 (2
(H, d, J = 8Hz), 6.86 (2H, d, J = 8Hz), 7.36 (3H, m), 7.50
(2H, m)

Example 78 In the same manner as in Example 1- (1), 2-amino-2-
[2- [4- [4- (Dimethylphenylsilyl) butyl] aminophenyl] ethyl] -1,3-propanediol was obtained. NMR (DMSO-d ₆ , δ): 0.25 (6H, s), 0.77 (2
H, m), 1.3-1.6 (8H, m), 2.41 (2H, m), 2.92 (2H, m), 3.2
2 (4H, m), 4.42 (2H, br s), 5.20 (1H, t, J = 6Hz), 6.45
(2H, d, J = 8Hz), 6.88 (2H, d, J = 8Hz), 7.37 (3H, m), 7.51
(2H, m)

Production Example 79 (1) In the same manner as in Production Example 40- (4), 2- [2-
Diethyl [4- [4- [dimethyl (1-naphthyl) silyl] butyl] aminophenyl] ethyl] malonate was obtained. NMR (DMSO-d ₆ , δ): 0.42 (6H, s), 0.98 (2
H, m), 1.18 (6H, t, J = 7Hz), 1.3-1.6 (4H, m), 1.97 (2H,
m), 2.39 (2H, t, J = 7Hz), 2.90 (2H, m), 3.35 (1H, t, J = 7
Hz), 4.11 (4H, q, J = 7Hz), 5.28 (1H, t, J = 6Hz), 6.42 (2
(H, d, J = 8Hz), 6.83 (2H, d, J = 8Hz), 7.45-7.6 (3H, m), 7.6
8 (1H, d, J = 7Hz), 7.94 (2H, d, J = 8Hz), 8.07 (1H, d, J = 8H)
z)

(2) In the same manner as in Production Example 3- (6),
2-amino-2- [2- [4- [4- [dimethyl (1-
Naphthyl) silyl] butyl] aminophenyl] ethyl]
Diethyl malonate was obtained. NMR (DMSO-d ₆ , δ): 0.42 (6H, s), 0.98 (2
H, m), 1.18 (6H, t, J = 7Hz), 1.3-1.6 (4H, m), 1.98 (2H,
m), 2.27 (2H, s), 2.35 (2H, m), 2.89 (2H, m), 4.11 (4
H, q, J = 7Hz), 5.24 (1H, t, J = 6Hz), 6.41 (2H, d, J = 8Hz),
6.83 (2H, d, J = 8Hz), 7.45-7.6 (3H, m), 7.67 (1H, d, J = 7
Hz), 7.93 (2H, d, J = 8Hz), 8.07 (1H, d, J = 7Hz)

Example 79 In the same manner as in Example 1- (1), 2-amino-2-
[2- [4- [4- [Dimethyl (1-naphthyl) silyl] butyl] aminophenyl] ethyl] -1,3-propanediol was obtained. NMR (DMSO-d ₆ , δ): 0.43 (6H, s), 0.99 (2
H, m), 1.3-1.6 (8H, m), 2.40 (2H, m), 2.88 (2H, m), 3.2
0 (4H, m), 4.41 (2H, br s), 5.17 (1H, t, J = 6Hz), 6.40
(2H, d, J = 8Hz), 6.84 (2H, d, J = 8Hz), 7.45-7.6 (3H, m),
7.68 (1H, d, J = 7Hz), 7.93 (2H, d, J = 8Hz), 8.08 (1H, d, J
= 8Hz)

Production Example 80 (1) In the same manner as in Production Example 68- (4), 2- [4-
[7- (Trimethylsilyl) heptyl] phenyl] ethanol was obtained. NMR (CDCl ₃ , δ): -0.03 (9H, s), 0.48 (2H, b
r), 1.32 (8H, br), 1.60 (2H, br), 2.59 (2H, t, J = 7Hz),
2.86 (2H, t, J = 7Hz), 3.87 (2H, br), 7.15 (4H, s)

(2) 7- [4- (2-Iodoethyl) phenyl] heptyltrimethylsilane was obtained in the same manner as in Production Example 19- (4). NMR (CDCl ₃ , δ): -0.03 (9H, s), 0.47 (2H, b
r), 1.28 (8H, br), 1.57 (2H, br), 2.57 (2H, t, J = 7Hz),
3.13 (2H, t, J = 7Hz), 3.31 (2H, t, J = 7Hz), 7.10 (4H, m)

(3) In the same manner as in Production Example 52- (5), diethyl 2- [2- [4- [7- (trimethylsilyl) heptyl] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): -0.03 (9H, s), 0.47 (2H, b
r), 1.27 (6H, t, J = 7Hz), 1.25-1.35 (8H, br), 1.58 (2H,
br), 2.17-2.25 (2H, m), 2.51-2.65 (4H, m), 3.33 (1H,
t, J = 7Hz), 4.19 (4H, q, J = 7Hz), 7.09 (4H, s) ESMS (m / z): 435,457

(4) In the same manner as in Production Example 3- (6),
Diethyl 2-amino-2- [2- [4- [7- (trimethylsilyl) heptyl] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): -0.05 (9H, s), 0.47 (2H, b
r), 1.27 (6H, t, J = 7Hz), 1.22-1.35 (8H, br), 1.58 (4H,
br), 2.20-2.27 (2H, m), 2.52-2.66 (4H, m), 4.21 (4H,
q, J = 7Hz), 7.08 (4H, s) ESMS (m / z): 450

Example 80 (1) In the same manner as in Example 1- (1), 2-amino-
2- [2- [4- [7- (Trimethylsilyl) heptyl] phenyl] ethyl] -1,3-propanediol was obtained. NMR (DMSO-d ₆ , δ): -0.05 (9H, s), 0.47
(2H, br), 1.28 (10H, br), 1.44-1.58 (4H, br), 2.48-2.5
8 (4H, br), 3.23 (4H, br), 4.45 (2H, br), 7.07 (4H, s) ESMS (m / z): 366

(2) In the same manner as in Example 26- (2), 2-amino-2- [2- [4- [7- (trimethylsilyl) heptyl] phenyl] ethyl] -1,3-propanediol The hydrochloride was obtained. NMR (CDCl ₃ , δ): -0.03 (9H, s), 0.45 (2H, b
r), 1.27 (8H, br), 1.53 (2H, br), 1.76 (2H, br), 2.50-
2.60 (4H, br), 3.51 (4H, d, J = 7Hz), 5.37 (2H, t, J = 7H
z), 7.10 (4H, s), 7.82 (3H, br) ESMS (m / z): 366

Production Example 81 (1) In the same manner as in Production Example 52- (2), 2- [2-
[4- [5- (Trimethylsilyl) pentyl] phenyl] ethoxy] tetrahydropyran was obtained. NMR (CDCl ₃ , δ): -0.05 (9H, s), 0.47 (2H,
m), 1.32 (6H, br), 1.45-1.90 (6H, m), 2.56 (2H, t, J = 7
Hz), 2.87 (2H, d, J = 7Hz), 3.40-3.50 (1H, br), 3.57-3.
66 (1H, m), 3.73-3.82 (1H, br), 3.89-3,93 (1H, m), 4.
59 (1H, br), 7.08 (2H, d, J = 8Hz), 7.16 (2H, d, J = 8Hz)

(2) In the same manner as in Preparation Example 68- (4), 2- [4- [5- (trimethylsilyl) pentyl]
[Phenyl] ethanol was obtained. NMR (CDCl ₃ , δ): -0.05 (9H, s), 0.47 (2H, b
r), 1.28-1.40 (4H, br), 1.55-1.66 (2H, br), 2.57 (2H,
t, J = 7Hz), 2.85 (2H, t, J = 7Hz), 3.84 (2H, br), 7.12 (4
H, s)

(3) In the same manner as in Production Example 19- (4), 5- [4- (2-iodoethyl) phenyl] pentyltrimethylsilane was obtained. NMR (CDCl ₃ , δ): -0.04 (9H, s), 0.47 (2H, b
r), 1.27-1.42 (4H, br), 1.55-1.66 (2H, br), 2.57 (2H,
(t, J = 7Hz), 3.15 (2H, t, J = 7Hz), 3.35 (2H, t, J = 7Hz), 7.
10 (4H, m)

(4) In the same manner as in Production Example 52- (5), diethyl 2- [2- [4- [5- (trimethylsilyl) pentyl] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): -0.04 (9H, s), 0.48 (2H, b
r), 1.27 (6H, t, J = 7Hz), 1.33 (4H, br), 1.60 (2H, br),
2.21 (2H, m), 2.54-2.67 (4H, m), 3.35 (1H, t, J = 7Hz),
4.21 (4H, q, J = 7Hz), 7.10 (4H, s) ESMS (m / z): 405

(5) In the same manner as in Production Example 3- (6),
Diethyl 2-amino-2- [2- [4- [5- (trimethylsilyl) pentyl] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): -0.03 (9H, s), 0.48 (2H, b
r), 1.28 (6H, t, J = 7Hz), 1.24-1.40 (4H, br), 1.60 (2H,
br), 2.21-2.30 (2H, m), 2.53-2.68 (4H, m), 4.22 (4H,
q, J = 7Hz), 7.11 (4H, s) ESMS (m / z): 422

Example 81 (1) In the same manner as in Example 1- (1), 2-amino-
2- [2- [4- [5- (Trimethylsilyl) pentyl] phenyl] ethyl] -1,3-propanediol was obtained. NMR (DMSO-d ₆ , δ): -0.05 (9H, s), 0.45
(2H, br), 1.28 (6H, br), 1.43-1.60 (4H, m), 2.47-2.56
(4H, m), 3.23 (4H, br), 4.43 (2H, br), 7.07 (4H, s) ESMS (m / z): 338

(2) In the same manner as in Example 26- (2), 2-amino-2- [2- [4- [5- (trimethylsilyl) pentyl] phenyl] ethyl] -1,3-propanediol The hydrochloride was obtained. NMR (DMSO-d ₆ , δ): -0.03 (9H, s), 0.47
(2H, br), 1.30 (4H, br), 1.49-1.60 (2H, br), 1.74-1.83
(2H, br), 2.50-2.63 (4H, br), 3.53 (4H, br), 5.39 (2
H, br), 7.11 (4H, s), 7.80 (3H, br) ESMS (m / z): 338

Production Example 82 (1) In the same manner as in Production Example 74- (3), 2- [2-
Diethyl (4-allyloxyphenyl) ethyl] malonate was obtained. NMR (CDCl ₃ , δ): 1.29 (6H, t, J = 7Hz), 2.18
(2H, dt, J = 7,7Hz), 2.59 (2H, t, J = 7Hz), 3.32 (1H, t, J = 7H
z), 4.19 (4H, q, J = 7Hz), 4.50 (2H, d, J = 4Hz), 5.28 (1
(H, d, J = 10Hz), 5.40 (1H, d, J = 15Hz), 5.97-6.12 (1H, m),
6.84 (2H, d, J = 8Hz), 7.08 (2H, d, J = 8Hz)

(2) In the same manner as in Production Example 40- (4), diethyl 2- [2- [4- [3- (dimethylphenylsilyl) propoxy] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): 0.29 (6H, s), 0.87 (2H, b
r), 1.27 (6H, t, J = 7Hz), 1.70-1.85 (2H, br), 2.18 (2H,
m), 2.59 (2H, m), 3.32 (1H, t, J = 7Hz), 3.85 (2H, t, J = 7
Hz), 4.18 (4H, q, J = 7Hz), 6.78 (2H, d, J = 8Hz), 7.07 (2
(H, d, J = 8Hz), 7.34 (3H, m), 7.52 (2H, m)

(3) In the same manner as in Production Example 3- (6),
Diethyl 2-amino-2- [2- [4- [3- (dimethylphenylsilyl) propoxy] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): 0.29 (6H, s), 0.85 (2H, b
r), 1.27 (6H, t, J = 7Hz), 1.75-1.84 (2H, br), 2.02 (2H,
br), 2.21 (2H, m), 2.58 (2H, m), 3.85 (2H, t, J = 7Hz),
4.20 (4H, q, J = 7Hz), 6.77 (2H, d, J = 8Hz), 7.07 (2H, d, J
= 8Hz), 7.35 (3H, m), 7.52 (2H, m) ESMS (m / z): 472

Example 82 (1) In the same manner as in Example 1- (1), 2-amino-
2- [2- [4- [3- (Dimethylphenylsilyl) propoxy] phenyl] ethyl] -1,3-propanediol was obtained. NMR (DMSO-d ₆ , δ): 0.25 (6H, s), 0.81 (2
H, m), 1.43 (2H, m), 1.65 (2H, m), 2.47 (2H, m), 3.20
(4H, br), 3.83 (2H, t, J = 7Hz), 4.42 (2H, br), 6.75 (2
(H, d, J = 8Hz), 7.03 (2H, d, J = 8Hz), 7.33 (3H, m), 7.50
(2H, m)

(2) In the same manner as in Example 26- (2), 2-amino-2- [2- [4- [3- (dimethylphenylsilyl) propoxy] phenyl] ethyl] -1,
3-Propanediol hydrochloride was obtained.

Production Example 83 (1) In the same manner as in Production Example 40- (4), 2- [2-
[4- [3- (benzyldimethylsilyl) propoxy]
There was obtained diethyl [phenyl] ethyl] malonate. NMR (CDCl ₃ , δ): 0.00 (6H, s), 0.60 (2H,
m), 1.27 (6H, t, J = 6Hz), 1.76 (2H, m), 2.11 (2H, s),
2.18 (2H, q, J = 6Hz), 2.60 (2H, t, J = 6Hz), 3.32 (1H, t, J
= 6Hz), 3.86 (2H, t, J = 6Hz), 4.20 (4H, q, J = 6Hz), 6.80
(2H, d, J = 8Hz), 6.96-7.12 (5H, m), 7.21 (2H, t, J = 8Hz) ES-MS (m / z): 469 (MH)

(2) In the same manner as in Production Example 3- (6),
Diethyl 2-amino-2- [2- [4- [3- (benzyldimethylsilyl) propoxy] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): 0.00 (6H, s), 0.60 (2H,
m), 1.28 (6H, t, J = 6Hz), 1.75 (2H, m), 2.03 (2H, br
s), 2.11 (2H, s), 2.22 (2H, m), 2.60 (2H, m), 3.86 (2
H, t, J = 6Hz), 4.22 (4H, q, J = 6Hz), 6.80 (2H, d, J = 8Hz),
6.96-7.12 (5H, m), 7.21 (2H, t, J = 8Hz) ES + MS (m / z): 486 (M + H)

Example 83 (1) In the same manner as in Example 1- (1), 2-amino-
2- [2- [4- [3- (benzyldimethylsilyl) propoxy] phenyl] ethyl] -1,3-propanediol was obtained. NMR (CDCl ₃ , δ): 0.00 (6H, s), 0.60 (2H,
m), 1.63-1.82 (4H, m), 2.11 (2H, s), 2.60 (2H, m), 3.
50 (2H, d, J = 11Hz), 3.60 (2H, d, J = 11Hz), 3.86 (2H, t, J
= 6Hz), 6.80 (2H, d, J = 8Hz), 6.97-7.12 (5H, m), 7.21
(2H, t, J = 8Hz) ES + MS (m / z): 402 (M + H)

(2) In the same manner as in Example 26- (2), 2-amino-2- [2- [4- [3- (benzyldimethylsilyl) propoxy] phenyl] ethyl] -1,
3-Propanediol hydrochloride was obtained. NMR (DMSO-d ₆ , δ): -0.04 (6H, s), 0.57
(2H, m), 1.60-1.80 (4H, m), 2.11 (2H, s), 2.54 (2H,
m), 3.52 (4H, d, J = 6Hz), 3.86 (2H, t, J = 6Hz), 5.37 (2H,
t, J = 6Hz), 6.84 (2H, d, J = 8Hz), 7.01 (2H, d, J = 8Hz), 7.
05 (1H, t, J = 8Hz), 7.11 (2H, d, J = 8Hz), 7.20 (2H, t, J = 8
Hz), 7.82 (3H, br s)

Production Example 84 (1) In the same manner as in Production Example 40- (4), 2- [2-
[4- [3- (methyldiphenylsilyl) propoxy]
There was obtained diethyl [phenyl] ethyl] malonate. NMR (CDCl ₃ , δ): 0.58 (3H, s), 1.19 (2H,
m), 1.27 (6H, t, J = 6Hz), 1.84 (2H, m), 2.18 (2H, q, J = 6
Hz), 2.59 (2H, t, J = 6Hz), 3.32 (1H, t, J = 6Hz), 3.89 (2
H, t, J = 6Hz), 4.20 (4H, q, J = 6Hz), 6.87 (2H, d, J = 8Hz),
7.06 (2H, d, J = 8Hz), 7.30-7.65 (10H, m) ES-MS (m / z): 517 (MH)

(2) In the same manner as in Production Example 3- (6),
Diethyl 2-amino-2- [2- [4- [3- (methyldiphenylsilyl) propoxy] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): 0.58 (3H, s), 1.19 (2H,
m), 1.28 (6H, t, J = 6Hz), 1.84 (2H, m), 2.04 (2H, br
s), 2.22 (2H, m), 2.59 (2H, m), 3.89 (2H, t, J = 6Hz), 4.
22 (4H, q, J = 6Hz), 6.78 (2H, d, J = 8Hz), 7.08 (2H, d, J = 8
Hz), 7.30-7.41 (6H, m), 7.49-7.58 (4H, m) ES + MS (m / z): 534 (M + H)

Example 84 In the same manner as in Example 1- (1), 2-amino-2-
[2- [4- [3- (Methyldiphenylsilyl) propoxy] phenyl] ethyl] -1,3-propanediol was obtained. NMR (CDCl ₃ , δ): 0.58 (3H, s), 1.19 (2H,
m), 1.66 (2H, m), 1.84 (2H, m), 2.58 (2H, m), 3.50 (2
H, d, J = 11Hz), 3.60 (2H, d, J = 11Hz), 3.89 (2H, t, J = 6H
z), 6.76 (2H, d, J = 8Hz), 7.07 (2H, d, J = 8Hz), 7.29-7.4
1 (6H, m), 7.47-7.56 (4H, m) ES + MS (m / z): 450 (M + H)

Production Example 85 (1) In the same manner as in Production Example 50- (3), 4- (3-butenyloxy) phenol was obtained from hydroquinone and 4-bromo-1-butene. NMR (CDCl ₃ , δ): 2.51 (2H, m), 3.96 (2H, t,
J = 6Hz), 4.56 (1H, s), 5.08-5.20 (2H, m), 5.90 (1H,
m), 6.71-6.84 (4H, m)

(2) 5- [4- (3-Butenyloxy) phenyloxymethyl] -2,2-dimethyl-5-nitro-1,3-dioxane was prepared in the same manner as in Production Example 50- (4). Obtained. NMR (CDCl ₃ , δ): 1.43 (3H, s), 1.46 (3H,
s), 2.51 (2H, q, J = 6Hz), 3.96 (2H, t, J = 6Hz), 4.16 (2H
(H, d, J = 14Hz), 4.37 (2H, s), 4.47 (2H, d, J = 14Hz), 5.06
-5.20 (2H, m), 5.90 (1H, m), 6.81 (4H, s)

(3) In the same manner as in Production Example 40- (4), 2,2-dimethyl-5- [4- (4-dimethylphenylsilylbutyloxy) phenyloxymethyl] -5
-Nitro-1,3-dioxane was obtained. NMR (CDCl ₃ , δ): 0.27 (6H, s), 0.80 (2H,
m), 1.42 (3H, s), 1.44 (3H, s), 1.46 (2H, m), 1.76 (2
H, m), 3.88 (2H, t, J = 6Hz), 4.16 (2H, d, J = 14Hz), 4.36
(2H, s), 4.48 (2H, d, J = 14Hz), 6.78 (4H, s), 7.30-7.54
(5H, m)

(4) In the same manner as in Production Example 50- (5), 5-amino-2,2-dimethyl-5- [4- (4-
Dimethylphenylsilylbutyloxy) phenyloxymethyl] -1,3-dioxane was obtained. NMR (CDCl ₃ , δ): 0.27 (6H, s), 0.80 (2H,
m), 1.42 (3H, s), 1.48 (3H, s), 1.50 (2H, m), 1.76 (2
H, m), 3.62 (2H, t, J = 6Hz), 3.82-3.97 (6H, m), 6.76-6.
86 (4H, m), 7.32-7.38 (3H, m), 7.47-7.53 (2H, m)

Example 85 In the same manner as in Example 50, 2-amino-2- [4-
(4-Dimethylphenylsilylbutyloxy) phenyloxymethyl] -1,3-propanediol hydrochloride was obtained. NMR (DMSO-d ₆ , δ): 0.24 (6H, s), 0.78 (2
H, m), 1.41 (2H, m), 1.69 (2H, m), 3.62 (4H, d, J = 6Hz),
3.86 (2H, t, J = 6Hz), 3.98 (2H, s), 5.43 (2H, brs), 6.
80-6.92 (4H, m), 7.32-7.38 (3H, m), 7.47-7.53 (2H,
m), 8.07 (3H, br s)

Production Example 86 (1) In the same manner as in Production Example 40- (4), 5- [4-
(4-butyldimethylsilylbutyloxy) phenyloxymethyl] -2,2-dimethyl-5-nitro-1,3
-Dioxane was obtained. NMR (CDCl ₃ , δ): -0.04 (6H, s), 0.45-0.57
(4H, m), 0.87 (3H, t, J = 6Hz), 1.20-1.36 (4H, m), 1.44
(3H, s), 1.46 (3H, s), 1.50 (2H, m), 1.77 (2H, m), 3.9
0 (2H, t, J = 6Hz), 4.16 (2H, d, J = 14Hz), 4.36 (2H, s),
4.48 (2H, d, J = 14Hz), 6.81 (4H, s)

(2) In the same manner as in Production Example 50- (5), 5-amino-5- [4- (4-butyldimethylsilylbutyloxy) phenyloxymethyl] -2,2-dimethyl-1, 3-Dioxane was obtained. NMR (CDCl ₃ , δ): 0.04 (6H, s), 0.49-0.61
(4H, m), 0.91 (3H, t, J = 6Hz), 1.24-1.40 (4H, m), 1.48
(3H, s), 1.50 (2H, m), 1.52 (3H, s), 1.81 (2H, m), 3.6
7 (2H, d, J = 14Hz), 3.90-4.00 (6H, m), 6.87 (4H, s)

Example 86 In the same manner as in Example 50, 2-amino-2- [4-
(4-butyldimethylsilylbutyloxy) phenyloxymethyl] -1,3-propanediol hydrochloride was obtained. NMR (CDCl ₃ , δ): -0.04 (6H, s), 0.45-0.56
(4H, m), 0.86 (3H, t, J = 6Hz), 1.20-1.47 (6H, m), 1.70
(2H, s), 3.64 (4H, d, J = 6Hz), 3.90 (2H, t, J = 6Hz), 3.99
(2H, s), 5.45 (2H, t, J = 6Hz), 6.88 (4H, s), 8.08 (3H,
s)

Production Example 87 (1) In the same manner as in Production Example 40- (4), 2,2-dimethyl-5- [4- (4-dimethylpentylsilylbutyloxy) phenyloxymethyl] -5-nitro -1,
3-Dioxane was obtained. NMR (CDCl ₃ , δ): 0.04 (6H, s), 0.48-0.62
(4H, m), 0.92 (3H, t, J = 6Hz), 1.26-1.38 (6H, m), 1.48
(3H, s), 1.50 (3H, s), 1.52 (2H, m), 1.81 (2H, m), 3.9
4 (2H, t, J = 6Hz), 4.20 (2H, d, J = 14Hz), 4.40 (2H, s),
4.52 (2H, d, J = 14Hz), 6.85 (4H, s)

(2) In the same manner as in Production Example 50- (5), 5-amino-2,2-dimethyl-5- [4- (4-
Dimethylpentylsilylbutyloxy) phenyloxymethyl] -1,3-dioxane was obtained. NMR (CDCl ₃ , δ): 0.04 (6H, s), 0.48-0.62
(4H, m), 0.92 (3H, t, J = 6Hz), 1.28-1.38 (6H, m), 1.48
(3H, s), 1.50 (2H, m), 1.52 (3H, s), 1.81 (2H, m), 3.6
7 (2H, d, J = 14Hz), 3.90-4.00 (6H, m), 6.87 (4H, s)

Example 87 In the same manner as in Example 50, 2-amino-2- [4-
(4-Dimethylpentylsilylbutyloxy) phenyloxymethyl] -1,3-propanediol hydrochloride was obtained. NMR (DMSO-d ₆ , δ): -0.04 (6H, s), 0.44-
0.58 (4H, m), 0.86 (3H, t, J = 6Hz), 1.22-1.33 (6H, m),
1.42 (2H, m), 1.70 (2H, m), 3.62 (4H, d, J = 4Hz), 3.89
(2H, t, J = 6Hz), 3.98 (2H, s), 5.44 (2H, t, J = 4Hz), 6.88
(4H, s), 8.05 (3H, br s)

Production Example 88 (1) In the same manner as in Production Example 40- (4), 5- [4-
(4-benzyldimethylsilylbutyloxy) phenyloxymethyl] -2,2-dimethyl-5-nitro-1,
3-Dioxane was obtained. NMR (CDCl ₃ , δ): 0.03 (6H, s), 0.58 (2H,
m), 1.46 (3H, s), 1.48 (2H, m), 1.49 (3H, s), 1.78 (2
H, m), 2.12 (2H, s), 3.91 (2H, t, J = 6Hz), 4.20 (2H, d, J
= 14Hz), 4.40 (2H, s), 4.50 (2H, d, J = 14Hz), 6.83 (4H,
s), 7.02 (2H, d, J = 8Hz), 7.09 (1H, t, J = 8Hz), 7.22 (2
(H, t, J = 8Hz)

(2) In the same manner as in Production Example 50- (5), 5-amino-5- [4- (4-benzyldimethylsilylbutyloxy) phenyloxymethyl] -2,2-
Dimethyl-1,3-dioxane was obtained. NMR (CDCl ₃ , δ): 0.03 (6H, s), 0.58 (2H,
m), 1.46 (3H, s), 1.49 (2H, m), 1.51 (3H, s), 1.78 (2
H, m), 2.12 (2H, s), 3.66 (2H, d, J = 14Hz), 3.88-3.99
(3H, m), 6.86 (4H, s), 7.01 (2H, d, J = 8Hz), 7.09 (1H,
(t, J = 8Hz), 7.22 (2H, t, J = 8Hz)

Example 88 In the same manner as in Example 50, 2-amino-2- [4-
(4-Benzyldimethylsilylbutyloxy) phenyloxymethyl] -1,3-propanediol hydrochloride was obtained. NMR (DMSO-d ₆ , δ): -0.07 (6H, s), 0.51
(2H, m), 1.40 (2H, m), 1.67 (2H, m), 2.08 (2H, s), 3.6
2 (4H, d, J = 4Hz), 3.87 (2H, t, J = 6Hz), 3.98 (2H, s), 5.
44 (2H, t, J = 4Hz), 6.88 (4H, s), 6.95-7.08 (3H, m), 7.
17 (2H, t, J = 8Hz), 8.08 (3H, s)

Production Example 89 (1) Dimethylphenylsilane (770 mg) and 2
-[2- [4- (4-pentenyl) phenyl] ethyl]
Hexachloroplatinic (IV) acid hexahydrate (19 mg) was added to a mixture of diethyl malonate (1.20 g) at room temperature, and the mixture was stirred at 100 ° C. for 2 hours. The mixture was purified by silica gel column chromatography (ethyl acetate-hexane, 1:19) to give diethyl 2- [2- [4- (5-dimethylphenylsilylpentyl) phenyl] ethyl] malonate (1.4 g). Was. NMR (CDCl ₃ , δ): 0.24 (6H, s), 0.68-0.78
(2H, m), 1.26 (6H, t, J = 7.5Hz), 1.3-1.4 (4H, m), 1.5-
1.6 (2H, m), 2.15-2.25 (2H, m), 2.45-2.55 (2H, m), 2.
55-2.65 (2H, m), 3.32 (1H, t, J = 7.0Hz), 4.16 (4H, q, J =
7.5Hz), 7.05-7.1 (4H, m), 7.3-7.35 (3H, m), 7.45-7.5
(2H, m)

(2) To a suspension of sodium hydride (143 mg) in N, N-dimethylformamide (30 ml) was added
-Diethyl 2- [2- [4- (5-dimethylphenylsilylpentyl) phenyl] ethyl] malonate (1.4 g)
Was added at room temperature and the mixture was stirred for 30 minutes. To this solution was added O- (2,4-dinitrophenyl) hydroxylamine (595 mg) at room temperature and the mixture was stirred for 3 hours. The mixture was poured into ethyl acetate, washed with half-saturated saline and brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate-hexane, 1: 9) to give 2-amino-
Diethyl 2- [2- [4- (5-dimethylphenylsilylpentyl) phenyl] ethyl] malonate (0.90
g) was obtained. NMR (CDCl ₃ , δ): 0.24 (6H, s), 0.70-0.78
(2H, m), 1.26 (6H, t, J = 7.5Hz), 1.3-1.36 (4H, m), 1.5-
1.6 (2H, m), 2.2-2.3 (2H, m), 2.5-2.6 (2H, m), 2.55-
2.65 (2H, m), 4.2 (4H, q, J = 7.5Hz), 7.0-7.1 (4H, m),
7.3-7.35 (3H, m), 7.45-7.5 (2H, m)

Example 89 A solution of diethyl 2-amino-2- [2- [4- (5-dimethylphenylsilylpentyl) phenyl] ethyl] malonate (0.90 g) in ethanol (18 ml) was treated with lithium borohydride ( 81 mg) was added at room temperature and the mixture was stirred overnight. Water (40 ml) was added to the solution and the mixture was stirred for 2 hours. Ethyl acetate was added and the mixture was washed with brine, dried over magnesium sulfate and concentrated under reduced pressure. The residue solid was triturated with diethyl ether to give 2-amino-2- [2- [4- (5-dimethylphenylsilylpentyl) phenyl] ethyl] -1,3-propanediol (330 mg). Melting point: 98-101 ° C NMR (CDCl ₃ , δ): 0.24 (6H, s), 0.68-0.78
(2H, m), 1.26-1.36 (4H, m), 1.5-1.6 (2H, m), 1.65-1.7
5 (2H, m), 2.48-2.6 (8H, m), 3.52 (4H, ABq), 7.0-7.05
(4H, m), 7.3-7.35 (3H, m), 7.45-7.5 (2H, m)

Production Example 90 (1) In the same manner as in Production Example 52- (2), 2- [2-
[4- (2-Propenyl) phenyl] ethoxy] tetrahydropyran was obtained. NMR (CDCl ₃ , δ): 1.4-1.9 (6H, m), 2.9 (2H,
t, J = 7.0Hz), 3.36 (2H, d, J = 7.0Hz), 3.42-3.50 (1H, m),
3.58-3.66 (1H, m), 3.72-3.80 (1H, m), 3.9-4.0 (1H, m
m), 4.6 (1H, m), 5.02-5.10 (2H, m), 5.9-6.05 (1H, m),
7.12 (4H, ABq)

(2) In the same manner as in Production Example 52- (3), 2- [4- (2-propenyl) phenyl] ethanol was obtained. NMR (CDCl ₃ , δ): 2.85 (2H, t, J = 7.0Hz), 3.3
6 (2H, d, J = 7.0Hz), 3.82 (2H, q, J = 7.0Hz), 5.02-5.12 (2
H, m), 5.9-6.04 (1H, m), 7.1-7.18 (4H, m)

(3) In the same manner as in Production Example 52- (4), 2- [4- (2-propenyl) phenyl] ethyl
I got iodide. NMR (CDCl ₃ , δ): 3.12-3.2 (2H, m), 3.3-3.4
(4H, m), 5.0-5.1 (2H, m), 5.9-6.04 (1H, m), 7.1-7.2
(4H, m)

(4) In the same manner as in Production Example 52- (5), diethyl 2- [2- [4- (2-propenyl) phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): 1.28 (6H, t, J = 7.5Hz), 2.1
6-2.26 (2H, m), 2.58-2.68 (2H, m), 3.3-3.4 (3H, m),
4.2 (4H, q, J = 7.5Hz), 5.02-5.1 (2H, m), 5.9-6.02 (1H,
m), 7.08-7.12 (4H, m)

(5) In the same manner as in Production Example 40- (4), diethyl 2- [2- [4- (3-dimethylphenylsilylpropyl) phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): 0.24 (6H, s), 0.76-0.82
(2H, m), 1.26 (6H, t, J = 7.5Hz), 1.58-1.66 (2H, m), 2.1
6-2.26 (2H, m), 2.55-2.70 (4H, m), 3.33 (1H, t, J = 7.0H
z), 4.2 (4H, q, J = 7.5Hz), 7.05-7.1 (4H, m), 7.3-7.35
(3H, m), 7.46-7.52 (2H, m)

(6) In the same manner as in Production Example 3- (6),
Diethyl 2-amino-2- [2- [4- (3-dimethylphenylsilylpropyl) phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): 0.24 (6H, s), 0.76-0.82
(2H, m), 1.26 (6H, t, J = 7.5Hz), 1.58-1.66 (2H, m), 2.1
8-2.28 (2H, m), 2.55-2.70 (4H, m), 4.2 (4H, q, J = 7.5H
z), 7.0-7.1 (4H, m), 7.3-7.35 (3H, m), 7.46-7.52 (2
H, m)

Example 90 By a method similar to that in Examples 1- (1) and 26- (2), 2-amino-2- [2- [4- (3-dimethylphenylsilylpropyl) phenyl] ethyl ] -1, 3-
Propanediol hydrochloride was obtained. NMR (DMSO-d ₆ , δ): 0.24 (6H, s), 0.76-0.
82 (2H, m), 1.5-1.64 (2H, m), 1.74-1.84 (2H, m), 2.52
-2.62 (4H, m), 3.50 (4H, d, J = 7.0Hz), 5.40 (2H, t, J = 7.
0Hz), 7.0-7.1 (4H, m), 7.3-7.35 (3H, m), 7.46-7.52
(2H, m), 7.4-7.55 (3H, br s)

Production Example 91 (1) In the same manner as in Production Example 40- (4), 2- [2-
Diethyl [4- (4-dimethylphenylsilylbutyl) phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): 0.24 (6H, s), 0.76-0.82
(2H, m), 1.26 (6H, t, J = 7.5Hz), 1.3-1.42 (2H, m), 1.55
-1.65 (2H, m), 2.16-2.24 (2H, m), 2.5-2.7 (4H, m), 3.
32 (1H, t, J = 7.0Hz), 4.2 (4H, q, J = 7.5Hz), 7.0-7.1 (4
H, m), 7.3-7.35 (3H, m), 7.45-7.5 (2H, m)

(2) In the same manner as in Production Example 3- (6),
Diethyl 2-amino-2- [2- [4- (4-dimethylphenylsilylbutyl) phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): 0.24 (6H, s), 0.74-0.8 (2
H, m), 1.26 (6H, t, J = 7.5Hz), 1.3-1.4 (2H, m), 1.55-1.
65 (2H, m), 2.2-2.26 (2H, m), 2.5-2.6 (2H, m), 2.6-2.6
5 (2H, m), 4.2 (4H, q, J = 7.5Hz), 7.0-7.1 (4H, m), 7.3-
7.35 (3H, m), 7.45-7.55 (2H, m)

Example 91 By a method similar to that in Example 1- (1) and Example 26- (2), 2-amino-2- [2- [4- (4-dimethylphenylsilylbutyl) phenyl] ethyl was used. ] -1,3-propanediol hydrochloride was obtained. Melting point: 250 ° C. NMR (CDCl ₃ , δ): 0.22 (6H, s), 0.7-0.85 (2
H, m), 1.3-1.4 (2H, m), 1.45-1.55 (2H, m), 1.9-2.0 (2
H, m), 2.4-2.5 (2H, m), 2.5-2.6 (2H, m), 3.7-3.8 (4H,
m), 6.95 (4H, ABq), 7.25-7.3 (3H, m), 7.45-7.54 (2H,
m)

Production Example 92 (1) In the same manner as in Production Example 40- (4), 2- [2-
[4- (3-dimethylisopropylsilylpropoxy)
There was obtained diethyl [phenyl] ethyl] malonate. NMR (CDCl ₃ , δ): 0.06 (6H, s), 0.6-0.7 (2
H, m), 0.76-0.9 (1H, m), 0.98 (6H, d, J = 7.0Hz), 1.3 (6
(H, t, J = 7.5Hz), 1.75-1.85 (2H, m), 2.16-2.26 (2H, m),
2.56-2.66 (2H, m), 3.36 (1H, t, J = 7.0Hz), 3.9 (2H, t, J
= 7.0Hz), 4.42 (4H, q, J = 7.5Hz), 6.84 (2H, d, J = 8.0Hz),
7.08 (2H, d, J = 8.0Hz)

(2) In the same manner as in Production Example 3- (6),
Diethyl 2-amino-2- [2- [4- (3-dimethylisopropylsilylpropoxy) phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): 0.04 (6H, s), 0.6-0.7 (2
H, m), 0.76-0.9 (1H, m), 0.98 (6H, d, J = 7.5Hz), 1.3 (6
(H, t, J = 7.5Hz), 1.75-1.85 (2H, m), 2.1 (2H, s), 2.22-
2.3 (2H, m), 2.6-2.7 (2H, m), 3.9 (2H, t, J = 7.0Hz), 4.
22 (4H, t, J = 7.5Hz), 6.84 (2H, d, J = 8.0Hz), 7.1 (2H, d, J
= 8.0Hz)

Example 92 In the same manner as in Example 1- (1), 2-amino-2-
[2- [4- (3-Dimethylisopropylsilylpropoxy) phenyl] ethyl] -1,3-propanediol was obtained. NMR (DMSO-d ₆ , δ): -0.02 (6H, s), 0.6-0.
7 (2H, m), 0.75-0.9 (1H, m), 0.96 (6H, t, J = 7.0Hz), 0.
14-1.55 (2H, m), 0.7-1.8 (4H, m), 3.25-3.4 (4H, m),
3.9 (2H, t, J = 7Hz), 6.8 (2H, ABq), 7.1 (2H, ABq)

Production Example 93 (1) In the same manner as in Production Example 40- (4), 2- [2-
[4- [4-dimethyl (2-naphthyl) silylbutyl]
There was obtained diethyl [phenyl] ethyl] malonate. NMR (CDCl ₃ , δ): 0.28 (6H, t, J = 7.5Hz), 0.3
0 (6H, s), 0.8-0.9 (2H, m), 1.35-1.45 (2H, m), 1.55-
1.65 (2H, m), 2.15-2.25 (2H, m), 2.46-2.6 (4H, m), 3.
3 (1H, t, J = 7Hz), 4.16 (4H, q, J = 7.5Hz), 7.05-7.1 (4H,
m), 7.45-7.5 (2H, m), 7.55 (1H, d, J = 8.5Hz), 7.75-7.8
5 (3H, m), 7.96 (1H, s)

(2) In the same manner as in Production Example 3- (6),
Diethyl 2-amino-2- [2- [4- [4-dimethyl (2-naphthyl) silylbutyl] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): 0.28 (6H, t, J = 7.5Hz), 0.3
0 (6H, s), 0.8-0.9 (2H, m), 1.35-1.45 (2H, m), 1.55-
1.65 (2H, m), 2.15-2.25 (2H, m), 2.46-2.6 (4H, m), 4.
16 (4H, q, J = 7.5Hz), 7.05-7.1 (4H, m), 7.45-7.5 (2H,
m), 7.55 (1H, d, J = 8.5Hz), 7.75-7.85 (3H, m), 7.96 (1
H, s)

Example 93 In the same manner as in Example 1- (1), 2-amino-2-
[2- [4- [4-Dimethyl (2-naphthyl) silylbutyl] phenyl] ethyl] -1,3-propanediol was obtained. NMR (DMSO-d ₆ , δ): 0.24 (6H, s), 0.76-0.
82 (2H, m), 1.2-1.6 (6H, m), 2.52-2.62 (4H, m), 3.30
(4H, m), 4.3 (2H, m), 7.0-7.1 (4H, m), 7.46-7.52 (2H,
m), 7.5 (1H, d, J = 8.0Hz), 7.8-7.85 (3H, m), 7.95 (1H,
s)

Production Example 94 (1) In the same manner as in Production Example 40- (4), 2- [2-
Diethyl [4- [4- (3,4-dimethoxyphenyl) dimethylsilylbutyl] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): 0.24 (6H, s), 0.7-0.8 (2
H, m), 1.28 (6H, t, J = 7.52Hz), 1.35-1.45 (2H, m), 1.55
-1.65 (2H, m), 2.15-2.25 (2H, m), 2.5-2.65 (4H, m),
3.32 (1H, t, J = 7Hz), 3.9 (6H, s), 4.2 (4H, q, J = 7.5Hz),
6.86 (1H, d, J = 8.5Hz), 6.95 (1H, s), 7.0-7.1 (5H, m)

(2) In the same manner as in Production Example 3- (6),
Diethyl 2-amino-2- [2- [4- [4- (3,4-dimethoxyphenyl) dimethylsilylbutyl] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): 0.22 (6H, s), 0.7-0.8 (2
H, m), 1.26 (6H, t, J = 7.5Hz), 1.3-1.4 (2H, m), 1.55-1.
65 (2H, m), 2.0 (2H, s), 2.2-2.3 (2H, m), 2.5-2.65 (4
H, m), 3.84 (6H, s), 4.2 (4H, q, J = 7.5Hz), 6.88 (1H, d,
J = 8.0Hz), 6.94 (1H, s), 7.0-7.1 (5H, m)

Example 94 In the same manner as in Example 1- (1), 2-amino-2-
[2- [4- [4- (3,4-Dimethoxyphenyl) dimethylsilylbutyl] phenyl] ethyl] -1,3-propanediol was obtained. NMR (DMSO-d ₆ , δ): 0.24 (6H, s), 0.76-0.
82 (2H, m), 1.2-1.6 (6H, m), 2.52-2.62 (4H, m), 3.30
(4H, m), 3.75 (6H, s), 4.55 (2H, m), 6.95-7.4 (7H, m)

Production Example 95 (1) In the same manner as in Production Example 40- (4), 2- [2-
[4- [4-dimethyl (1-naphthyl) silylbutyl]
There was obtained diethyl [phenyl] ethyl] malonate. NMR (CDCl ₃ , δ): 0.24 (6H, s), 0.72-0.8 (2
H, m), 1.26 (6H, t, J = 7.5Hz), 1.34-1.42 (2H, m), 1.56-
1.64 (2H, m), 2.15-2.25 (2H, m), 2.5-2.65 (4H, m), 3.
34 (1H, t, J = 7Hz), 4.2 (4H, q, J = 7.5Hz), 7.0-7.1 (6H,
m), 7.3-7.4 (3H, m), 7.45-7.55 (2H, m)

(2) In the same manner as in Production Example 3- (6),
Diethyl 2-amino-2- [2- [4- [4-dimethyl (1-naphthyl) silylbutyl] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): 0.22 (6H, s), 0.7-0.8 (2
H, m), 1.26 (6H, t, J = 7.5Hz), 1.3-1.4 (2H, m), 1.55-1.
65 (2H, m), 2.0 (2H, s), 2.2-2.3 (2H, m), 2.5-2.65 (4
H, m), 4.2 (4H, q, J = 7.5Hz), 7.0-7.1 (6H, m), 7.3-7.4
(3H, m), 7.45-7.5 (2H, m)

Example 95 In the same manner as in Example 1- (1), 2-amino-2-
[2- [4- [4-Dimethyl (1-naphthyl) silylbutyl] phenyl] ethyl] -1,3-propanediol was obtained. NMR (DMSO-d ₆ , δ): 0.24 (6H, s), 0.76-0.
82 (2H, m), 1.2-1.6 (6H, m), 2.52-2.62 (4H, m), 3.30
(4H, m), 4.55 (2H, m), 7.0-7.1 (6H, m), 7.35-7.45 (3
H, m), 7.5-7.6 (2H, m)

Production Example 96 (1) In the same manner as in Production Example 68- (5), 2- [2-
Diethyl [4- [2- (dimethylphenylsilyl) ethoxy] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): 0.34 (6H, s), 1.26 (6H, t,
J = 7.5Hz), 1.37 (2H, t, J = 7.5Hz), 2.10-2.21 (2H, m),
2.52-2.62 (2H, m), 3.31 (2H, t, J = 7.5Hz), 4.02 (2H, t,
J = 7.5Hz), 4.18 (4H, q, J = 7.5Hz), 6.76 (2H, d, J = 7.5H
z), 7.06 (2H, d, J = 7.5Hz), 7.33-7.43 (3H, m), 7.50-7.
58 (2H, m) ES (m / z): 465

(2) In the same manner as in Production Example 3- (6),
Diethyl 2-amino-2- [2- [4- [2- (dimethylphenylsilyl) ethoxy] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): 0.34 (6H, s), 1.27 (6H, t,
J = 7.5Hz), 1.36 (2H, t, J = 7.5Hz), 2.03 (2H, br s), 2.1
8-2.26 (2H, m), 2.53-2.62 (4H, m), 4.02 (2H, t, J = 7.5H
z), 4.20 (4H, q, J = 7.5Hz), 6.74 (2H, d, J = 7.5Hz), 7.06
(2H, d, J = 7.5Hz), 7.32-7.39 (3H, m), 7.49-7.56 (2H, m) ES (m / z): 458

Example 96 (1) In the same manner as in Example 1- (1), 2-amino-
2- [2- [4- [2- (Dimethylphenylsilyl) ethoxy] phenyl] ethyl] -1,3-propanediol was obtained. _{Mp: 124~125 ℃ NMR (CDCl 3,} δ): 0.34 (6H, s), 1.35 (2H, t,
J = 7.5Hz), 1.62-1.71 (2H, m), 2.52-2.61 (2H, m), 3.50
(2H, d, J = 10Hz), 3.60 (2H, d, J = 10Hz), 4.02 (2H, t, J =
7.5Hz), 6.75 (2H, d, J = 7.5Hz), 7.07 (2H, d, J = 7.5Hz),
7.33-7.40 (3H, m), 7.50-7.58 (2H, m) ES (m / z): 374

(2) In the same manner as in Example 26- (2), 2-amino-2- [2- [4- [2- (dimethylphenylsilyl) ethoxy] phenyl] ethyl] -1,3
-Propanediol hydrochloride was obtained. _{Mp: 106~109 ℃ NMR (CDCl 3,} δ): 0.30 (6H, s), 1.28 (2H, t,
J = 7.5Hz), 1.86-1.99 (2H, m), 2.49-2.60 (2H, m), 3.77
(4H, brs), 3.93 (2H, t, J = 7.5Hz), 6.67 (2H, d, J = 7.5H
z), 7.03 (2H, d, J = 7.5Hz), 7.29-7.36 (3H, m), 7.44-7.
52 (2H, m) ES (m / z): 374

Production Example 97 (1) In the same manner as in Production Example 68- (5), 2- [2-
Diethyl [4- [2- (butyldimethylsilyl) ethoxy] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): -0.05 (6H, s), 0.48-0.56
(2H, m), 0.84 (3H, t, J = 7.5Hz), 1.07 (2H, d, J = 7.5Hz),
1.17-1.35 (8H, m), 2.08-2.17 (2H, m), 2.54 (2H, d, J =
7.5Hz), 3.27 (1H, t, J = 7.5Hz), 3.97 (2H, d, J = 7.5Hz),
4.14 (4H, q, J = 7.5Hz), 6.75 (2H, d, J = 7.5Hz), 7.03 (2
(H, d, J = 7.5Hz) ES (m / z): 421

(2) In the same manner as in Production Example 3- (6),
Diethyl 2-amino-2- [2- [4- [2- (butyldimethylsilyl) ethoxy] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): -0.05 (6H, s), 0.49-0.58
(2H, m), 0.86 (3H, t, J = 7.5Hz), 1.09 (2H, d, J = 7.5Hz),
1.19-1.34 (8H, m), 2.01 (2H, br s), 2.15-2.25 (2H, m),
2.50-2.60 (2H, m), 4.00 (2H, d, J = 7.5Hz), 4.19 (4H, m
q, J = 7.5Hz), 6.76 (2H, d, J = 7.5Hz), 7.06 (2H, d, J = 7.5H
z) ES (m / z): 438

Example 97 (1) In the same manner as in Example 1- (1), 2-amino-
2- [2- [4- [2- (Butyldimethylsilyl) ethoxy] phenyl] ethyl] -1,3-propanediol was obtained. Melting point: 114-115 ° C NMR (CDCl ₃ , δ): -0.05 (6H, s), 0.50-0.57
(2H, m), 0.85 (3H, t, J = 7.5Hz), 1.09 (2H, t, J = 7.5Hz),
1.20-1.34 (4H, m), 1.62-1.71 (2H, m), 2.51-2.60 (2H,
m), 3.48 (2H, d, J = 10Hz), 3.58 (2H, d, J = 10Hz), 4.00
(2H, t, J = 7.5Hz), 6.77 (2H, d, J = 7.5Hz), 7.07 (2H, d, J =
7.5Hz) ES (m / z): 354

(2) In the same manner as in Example 26- (2), 2-amino-2- [2- [4- [2- (butyldimethylsilyl) ethoxy] phenyl] ethyl] -1,3-
Propanediol hydrochloride was obtained. _{Mp: 105~108 ℃ NMR (CDCl 3,} δ): - 0.02 (6H, s), 0.49-0.59
(2H, m), 0.88 (3H, t, J = 7.5Hz), 1.07 (2H, t, J = 7.5Hz),
1.22-1.39 (4H, m), 1.90-2.00 (2H, m), 2.51-2.62 (2H,
m), 3.80 (2H, br s), 3.95 (2H, t, J = 7.5Hz), 6.73 (2H,
d, J = 7.5 Hz), 7.07 (2H, d, J = 7.5 Hz) ES (m / z): 354

Production Example 98 (1) In the same manner as in Production Example 19- (4), 2- [4-
(4-Pentenyloxy) phenyl] ethyl iodide was obtained. NMR (CDCl ₃ , δ): 1.81-1.93 (2H, m), 2.18-
2.29 (2H, m), 3.10 (2H, t, J = 7Hz), 3.20 (2H, t, J = 7Hz),
3.96 (2H, t, J = 7Hz), 4.96-5.10 (2H, m), 5.85 (1H, m),
6.82 (2H, d, J = 8Hz), 7.09 (2H, d, J = 8Hz)

(2) In the same manner as in Production Example 74- (5), 2- [4- (4-pentenyloxy) phenyl] ethanol was obtained. NMR (CDCl ₃ , δ): 1.37 (3H, t, J = 7Hz), 1.81-
1.93 (2H, m), 2.17-2.29 (2H, m), 2.80 (2H, t, J = 7Hz),
3.76-3.87 (2H, m), 3.94 (2H, t, J = 7Hz), 4.96-5.10 (2
H, m), 5.85 (1H, m), 6.85 (2H, d, J = 8Hz), 7.11 (2H, d, J
= 8Hz)

(3) In the same manner as in Production Example 52- (5), diethyl 2- [2- [4- (4-pentenyloxy) phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): 1.26 (3H, t, J = 7Hz), 1.80-
1.91 (2H, m), 2.11-2.29 (4H, m), 2.59 (2H, br t, J = 7H
z), 3.31 (1H, t, J = 7Hz), 3.95 (2H, t, J = 7Hz), 4.19 (4
(H, q, J = 7Hz), 4.96-5.10 (2H, m), 5.84 (1H, m), 6.81 (2
H, d, J = 8Hz), 7.09 (2H, d, J = 8Hz) ES (m / z): 347

(4) In the same manner as in Production Example 40- (4), 2- [2- [4- [5- (butyldimethylsilyl)
There was obtained diethyl [pentoxy] phenyl] ethyl] malonate. NMR (CDCl ₃ , δ): -0.05 (6H, s), 0.45-0.57
(4H, m), 0.89 (3H, t, J = 7Hz), 1.20-1.54 (14H, m), 1.71
-1.85 (2H, m), 2.12-2.25 (2H, m), 2.56-2.64 (2H, m),
3.34 (1H, t, J = 7Hz), 3.93 (2H, t, J = 7Hz), 4.20 (4H, q, J
= 7Hz), 6.82 (2H, d, J = 8Hz), 7.09 (2H, d, J = 8Hz) ES (m / z): 463

(5) In the same manner as in Production Example 3- (6),
Diethyl 2-amino-2- [2- [4- [5- (butyldimethylsilyl) pentoxy] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): -0.05 (6H, s), 0.45-0.56
(4H, m), 0.89 (3H, t, J = 7Hz), 1.20-1.53 (14H, m), 1.70
-1.84 (2H, m), 2.18-2.28 (2H, m), 2.54-2.65 (2H, m),
3.92 (2H, t, J = 7Hz), 4.21 (4H, q, J = 7Hz), 6.81 (2H, d, J
= 7.5Hz), 7.10 (2H, d, J = 7.5Hz) ES (m / z): 480

Example 98 In the same manner as in Example 1- (1), 2-amino-2-
[2- [4- [5- (Butyldimethylsilyl) pentoxy] phenyl] ethyl] -1,3-propanediol was obtained. _{Mp: 102~105 ℃ NMR (CDCl 3 -CD} 3 OD, δ): - 0.05 (6H,
s), 0.45-0.56 (4H, m), 0.89 (3H, t, J = 7Hz), 1.20-1.51
(8H, m), 1.69-1.81 (4H, m), 2.50-2.60 (2H, m), 3.51
(2H, d, J = 10Hz), 3.63 (2H, d, J = 10Hz), 3.89 (2H, t, J = 7H
z), 6.80 (2H, d, J = 8Hz), 7.09 (2H, d, J = 8Hz) ES (m / z): 396

Production Example 99 (1) In the same manner as in Production Example 40- (4), 2- [2-
[4- [5- (dimethylphenylsilyl) pentoxy]
There was obtained diethyl [phenyl] ethyl] malonate. NMR (CDCl ₃ , δ): 0.25 (6H, s), 0.73-0.81
(2H, m), 1.27 (6H, t, J = 7Hz), 1.31-1.52 (4H, m), 1.66-
1.81 (2H, m), 2.12-2.23 (2H, m), 2.59 (2H, t, J = 7Hz),
3.32 (1H, t, J = 7Hz), 3.89 (2H, t, J = 7Hz), 4.20 (4H, q, J
= 7Hz), 6.79 (2H, d, J = 8Hz), 7.09 (2H, d, J = 8Hz), 7.31-
7.39 (3H, m), 7.48-7.53 (2H, m) ES (m / z): 483

(2) In the same manner as in Production Example 3- (6),
Diethyl 2-amino-2- [2- [4- [5- (dimethylphenylsilyl) pentoxy] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): 0.25 (6H, s), 0.73-0.80
(2H, m), 1.28 (6H, t, J = 7Hz), 1.31-1.52 (4H, m), 1.66-
1.80 (2H, m), 2.02 (2H, br s), 2.18-2.27 (2H, m), 2.5
3-2.63 (2H, m), 3.89 (2H, t, J = 7Hz), 4.21 (4H, q, J = 7H
z), 6.79 (2H, d, J = 8Hz), 7.09 (2H, d, J = 8Hz), 7.31-7.3
9 (3H, m), 7.48-7.53 (2H, m) ES (m / z): 500

Example 99 (1) In the same manner as in Example 1- (1), 2-amino-
2- [2- [4- [5- (Dimethylphenylsilyl) pentoxy] phenyl] ethyl] -1,3-propanediol was obtained. _{Mp: 103~106 ℃ NMR (CDCl 3,} δ): 0.25 (6H, s), 0.71-0.81
(2H, m), 1.30-1.80 (8H, m), 2.51-2.62 (2H, m), 3.50
(2H, d, J = 10Hz), 3.60 (2H, d, J = 10Hz), 3.89 (2H, t, J = 7H
z), 6.79 (2H, d, J = 8Hz), 7.08 (2H, d, J = 8Hz), 7.30-7.3
7 (3H, m), 7.46-7.53 (2H, m) ES (m / z): 416

(2) In the same manner as in Example 26- (2), 2-amino-2- [2- [4- [5- (dimethylphenylsilyl) pentoxy] phenyl] ethyl] -1,
3-Propanediol hydrochloride was obtained. _{Mp: 108~111 ℃ NMR (CDCl 3,} δ): 0.22 (6H, s), 0.68-0.78
(2H, m), 1.35-1.45 (4H, m), 1.59-1.71 (2H, m), 1.85-
2.00 (2H, m), 2.50-2.61 (2H, m), 3.70-3.85 (6H, m),
6.69 (2H, d, J = 8Hz), 7.04 (2H, d, J = 8Hz), 7.28-7.35 (3
H, m), 7.42-7.51 (2H, m) ES (m / z): 416

Production Example 100 (1) In the same manner as in Production Example 40- (4), 2- [2-
Diethyl [4- [3- (butyldimethylsilyl) propoxy] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): -0.01 (6H, s), 0.49-0.65
(4H, m), 0.89 (3H, t, J = 7Hz), 1.21-1.38 (10H, m), 1.70
-1.83 (2H, m), 2.12-2.24 (2H, m), 2.60 (2H, t, J = 7Hz),
3.34 (1H, t, J = 7Hz), 3.99 (2H, t, J = 7Hz), 4.20 (4H, q,
J = 7Hz), 6.81 (2H, d, J = 8Hz), 7.09 (2H, d, J = 8Hz) ES (m / z): 435

(2) In the same manner as in Production Example 3- (6),
Diethyl 2-amino-2- [2- [4- [3- (butyldimethylsilyl) propoxy] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): -0.01 (6H, s), 0.49-0.63
(4H, m), 0.89 (3H, t, J = 7Hz), 1.21-1.38 (10H, m), 1.70
-1.83 (2H, m), 2.19-2.28 (2H, m), 2.55-2.65 (2H, m),
3.89 (2H, t, J = 7Hz), 4.21 (4H, q, J = 7Hz), 6.81 (2H, d, J
= 8Hz), 7.09 (2H, d, J = 8Hz) ES (m / z): 452

Example 100 (1) In the same manner as in Example 1- (1), 2-amino-
2- [2- [4- [3- (Butyldimethylsilyl) propoxy] phenyl] ethyl] -1,3-propanediol was obtained. _{Mp: 104~107 ℃ NMR (CDCl 3 -CD} 3 OD, δ): - 0.01 (6H,
s), 0.49-0.63 (4H, m), 0.89 (3H, t, J = 7Hz), 1.21-1.38
(4H, m), 1.62-1.88 (4H, m), 2.54-2.63 (2H, m), 3.50
(2H, d, J = 10Hz), 3.62 (2H, br d, J = 10Hz), 3.89 (2H, t, J
= 7Hz), 6.82 (2H, d, J = 8Hz), 7.10 (2H, d, J = 8Hz) ES (m / z): 368

(2) In the same manner as in Example 26- (2), 2-amino-2- [2- [4- [3- (butyldimethylsilyl) propoxy] phenyl] ethyl] -1,3
-Propanediol hydrochloride was obtained. _{Mp: 105~110 ℃ NMR (CDCl 3 -CD} 3 OD, δ): - 0.01 (6H,
s), 0.49-0.63 (4H, m), 0.89 (3H, t, J = 7Hz), 1.21-1.39
(4H, m), 1.68-1.82 (2H, m), 1.92-2.03 (2H, m), 2.57-
2.68 (2H, m), 3.74-3.89 (6H, m), 6.89 (2H, d, J = 8Hz),
7.11 (2H, d, J = 8Hz) ES (m / z): 368

Production Example 101 (1) In the same manner as in Production Example 40- (4), 2- [2-
Diethyl [4- [3- (ethyldimethylsilyl) propoxy] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): -0.01 (6H, s), 0.47-0.65
(4H, m), 0.95 (3H, t, J = 7Hz), 1.29 (6H, t, J = 7Hz), 1.70
-1.85 (2H, m), 2.13-2.24 (2H, m), 2.60 (2H, t, J = 7Hz),
3.33 (1H, t, J = 7Hz), 3.89 (2H, t, J = 7Hz), 4.20 (4H, q,
J = 7Hz), 6.82 (2H, d, J = 8Hz), 7.09 (2H, d, J = 8Hz) ES (m / z): 409

(2) In the same manner as in Production Example 3- (6),
Diethyl 2-amino-2- [2- [4- [3- (ethyldimethylsilyl) propoxy] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): -0.01 (6H, s), 0.47-0.65
(4H, m), 0.94 (3H, t, J = 7Hz), 1.29 (6H, t, J = 7Hz), 1.52
-1.63 (2H, m), 1.70-1.85 (2H, m), 2.00-2.11 (2H, m),
2.20-2.29 (2H, m), 2.56-2.66 (2H, m), 3.89 (2H, t, J = 7
Hz), 4.23 (4H, q, J = 7Hz), 6.82 (2H, d, J = 8Hz), 7.11 (2
H, d, J = 8Hz) ES (m / z): 424

Example 101 In the same manner as in Example 1- (1), 2-amino-2-
[2- [4- [3- (Ethyldimethylsilyl) propoxy] phenyl] ethyl] -1,3-propanediol was obtained. _{Mp: 129~131 ℃ NMR (CDCl 3,} δ): - 0.01 (6H, s), 0.48-0.65
(4H, m), 0.95 (3H, t, J = 7Hz), 1.62-1.84 (4H, m), 2.55-
2.63 (2H, m), 3.50 (2H, d, J = 10Hz), 3.61 (2H, d, J = 10H
z), 3.89 (2H, t, J = 7Hz), 6.81 (2H, d, J = 8Hz), 7.10 (2
(H, d, J = 8Hz)

Production Example 102 (1) In the same manner as in Production Example 40- (4), 2- [2-
Diethyl [4- [4- (benzyldimethylsilyl) butoxy] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): -0.02 (6H, s), 0.51-0.60
(2H, m), 1.28 (6H, t, J = 7Hz), 1.40-1.58 (2H, m), 1.71-
1.83 (2H, m), 2.09 (2H, s), 2.13-2.23 (2H, m), 2.61 (2
(H, t, J = 7Hz), 3.33 (1H, t, J = 7Hz), 3.91 (2H, t, J = 7Hz),
4.19 (4H, q, J = 7Hz), 6.83 (2H, d, J = 8Hz), 6.97-7.11 (5
H, m), 7.14-7.23 (2H, m) ES (m / z): 483

(2) In the same manner as in Production Example 3- (6),
Diethyl 2-amino-2- [2- [4- [4- (benzyldimethylsilyl) butoxy] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): -0.02 (6H, s), 0.51-0.60
(2H, m), 1.28 (6H, t, J = 7Hz), 1.40-1.53 (2H, m), 1.71-
1.83 (2H, m), 1.99-2.11 (4H, m), 2.18-2.28 (2H, m),
2.55-2.65 (2H, m), 3.91 (2H, t, J = 7Hz), 4.22 (4H, q, J =
7Hz), 6.81 (2H, d, J = 8Hz), 6.95-7.33 (7H, m) ES (m / z): 500

Example 102 In the same manner as in Example 1- (1), 2-amino-2-
[2- [4- [4- (Benzyldimethylsilyl) butoxy] phenyl] ethyl] -1,3-propanediol was obtained. _{Mp: 90~91 ℃ NMR (CDCl 3,} δ): - 0.02 (6H, s), 0.50-0.60
(2H, m), 1.28 (6H, t, J = 7Hz), 1.39-1.55 (2H, m), 1.64-
1.85 (2H, m), 2.08 (2H, s), 2.55-2.65 (2H, m), 3.50 (2
H, d, J = 10Hz), 3.60 (2H, d, J = 10Hz), 3.91 (2H, t, J = 7H
z), 6.85 (2H, d, J = 8Hz), 6.97-7.24 (7H, m) ES (m / z): 416

Production Example 103 (1) In the same manner as in Production Example 40- (4), 2- [2-
Diethyl [4- [5- (butyldimethylsilyl) pentyl] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): -0.08 (6H, s), 0.49-0.59
(4H, m), 0.94 (3H, t, J = 7Hz), 1.26-1.48 (14H, m), 1.59
-1.71 (2H, m), 2.21-2.31 (2H, m), 2.59-2.73 (4H, m),
3.41 (1H, t, J = 7Hz), 4.25 (4H, q, J = 7Hz), 7.16 (4H, s) ES (m / z): 447

(2) In the same manner as in Production Example 3- (6),
Diethyl 2-amino-2- [2- [4- [5- (butyldimethylsilyl) pentyl] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): -0.08 (6H, s), 0.49-0.59
(4H, m), 0.94 (3H, t, J = 7Hz), 1.26-1.44 (13H, m), 1.57
-1.71 (4H, m), 2.10 (2H, br s), 2.25-2.35 (2H, m), 2.
58-2.73 (4H, m), 4.29 (4H, q, J = 7Hz), 7.17 (4H, s) ES (m / z): 464

Example 103 In the same manner as in Example 1- (1), 2-amino-2-
[2- [4- [5- (Butyldimethylsilyl) pentyl] phenyl] ethyl] -1,3-propanediol was obtained. _{Mp: 105~106 ℃ NMR (CDCl 3,} δ): - 0.08 (6H, s), 0.49-0.59
(4H, m), 0.94 (3H, t, J = 7Hz), 1.26-1.45 (8H, m), 1.58-
1.82 (6H, m), 2.58-2.73 (4H, m), 3.58 (2H, d, J = 10Hz),
3.68 (2H, d, J = 10Hz), 7.17 (4H, s) ES (m / z): 380

Production Example 104 (1) In the same manner as in Production Example 40- (4), 2- [2-
Diethyl [4- [5- (pentyldimethylsilyl) pentyl] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): -0.08 (6H, s), 0.49-0.59
(4H, m), 0.94 (3H, t, J = 7Hz), 1.29-1.46 (16H, m), 1.61
-1.71 (2H, m), 2.21-2.31 (2H, m), 2.59-2.73 (4H, m),
3.41 (1H, t, J = 7Hz), 4.25 (4H, q, J = 7Hz), 7.16 (4H, s) ES (m / z): 461

(2) In the same manner as in Production Example 3- (6),
Diethyl 2-amino-2- [2- [4- [5- (pentyldimethylsilyl) pentyl] phenyl] ethyl] malonate was obtained. NMR (CDCl ₃ , δ): -0.08 (6H, s), 0.48-0.59
(4H, m), 0.94 (3H, t, J = 7Hz), 1.28-1.46 (13H, m), 1.67
-1.71 (4H, m), 2.28-2.36 (2H, m), 2.58-2.73 (4H, m),
4.29 (4H, q, J = 7Hz), 7.16 (4H, s) ES (m / z): 478

Example 104 In the same manner as in Example 1- (1), 2-amino-2-
[2- [4- [5- (Pentyldimethylsilyl) pentyl] phenyl] ethyl] -1,3-propanediol was obtained. _{Mp: 102~103 ℃ NMR (CDCl 3,} δ): - 0.08 (6H, s), 0.48-0.59
(4H, m), 0.95 (3H, t, J = 7Hz), 1.29-1.46 (13H, m), 1.59
-1.81 (4H, m), 2.58-2.72 (2H, m), 3.58 (2H, d, J = 10H
z), 3.69 (2H, d, J = 10 Hz), 7.19 (4H, s) ES (m / z): 394

[0578]

The object compound (I) of the present invention and its pharmaceutically acceptable salts have pharmacological activities such as immunosuppressive activity and are useful as immunosuppressants.
Rejection by transplantation of organs or tissues such as heart, kidney, liver, bone marrow, skin, cornea, lung, pancreas, small intestine, limb, muscle, nerve; graft-versus-host disease by bone marrow transplantation; rheumatoid arthritis; systemic erythema It is useful for treating or preventing autoimmune diseases such as lupus erythematosus, Hashimoto's thyroiditis, multiple sclerosis, myasthenia gravis, type I diabetes and immune-related diseases such as psoriasis.

 ──────────────────────────────────────────────────続 き Continued on the front page (72) Inventor Seiji Yoshimura 4-21-2-1-404, Matsushiro, Tsukuba, Ibaraki Prefecture (72) Inventor Yoshito Abe 4-21-2-1-501, Matsushiro, Tsukuba, Ibaraki Prefecture ( 72) Inventor Tsuyoshi Mizutani 2-25-10-402 Matsushiro, Tsukuba City, Ibaraki Prefecture

Claims (6)

[Claims] 1. The formula: embedded image [Wherein, R ¹ represents a hydrogen atom or acyl, R ² represents a hydrogen atom, lower alkyl or aryl, R ³ represents a hydrogen atom, lower alkyl or higher alkyl, or R ² and R ³ are R ⁴ represents a hydrogen atom, a lower alkyl, a mono (or di or tri) halo (lower) alkyl, a higher alkyl, a lower alkenyl, a cyclo (lower) alkyl,
Represents an aryl optionally having one or more substituents, an aryl (lower) alkyl optionally having one or more substituents, or a heterocyclic group, and A represents a lower alkylene or a higher alkylene; an alkylene, E is bond, an oxygen atom or the formula -N (R ⁵⁾ - imino group represented by (wherein, R ⁵ is hydrogen atom or lower alkyl)
G represents a bond or an arylene, J represents a bond or an oxygen atom, and L represents a bond or a lower alkylene] and a pharmaceutically acceptable derivative thereof. Acceptable salt. 2. A pharmaceutical composition comprising, as an active ingredient, the compound according to claim 1 or a pharmaceutically acceptable salt thereof together with a pharmaceutically acceptable carrier and / or excipient. 3. Use of the compound according to claim 1 or a pharmaceutically acceptable salt thereof for the manufacture of a medicament. 4. The compound according to claim 1 or a pharmaceutically acceptable salt thereof for the manufacture of a medicament for treating or preventing rejection by transplantation, graft-versus-host disease by bone marrow transplantation, autoimmune disease or psoriasis. use. 5. An agent for treating or preventing rejection by transplantation, graft-versus-host disease by bone marrow transplantation, autoimmune disease or psoriasis, comprising the compound according to claim 1 or a pharmaceutically acceptable salt thereof. 6. An immunosuppressant comprising the compound according to claim 1 or a pharmaceutically acceptable salt thereof.