JP2000169458A - Method for producing agricultural and horticultural fungicides - Google Patents

Abstract

(57) [Problem] To provide an industrially advantageous production method of an amino acid amide derivative useful as an agricultural and horticultural fungicide. SOLUTION: General formula (1) (Wherein, R ¹ represents an alkyl group or the like, R ^{2 to} R ⁵ are the same,
Or may be different, and represents a hydrogen atom, an alkyl group, or the like, and X represents a hydrogen atom, an alkyl group, or the like. ) And a dipeptide derivative represented by the general formula (2): (Wherein Y ^{1 to} Y ⁴ may be the same or different and represent a hydrogen atom, a halogen atom, or the like, and Q represents a hydrogen atom, an alkali metal, and Y ^{1 to} Y ⁴ have the same substituents as in the general formula (2). Group And so on. By reacting with a 2-aminothiophenol derivative represented by the general formula (3): (Wherein, R ¹ , R ^{2 to} R ⁵ and Y ^{1 to} Y ⁴ have the same meanings as described above). The present invention provides a method for industrially easily producing an amino acid amide derivative useful as an agricultural and horticultural fungicide.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to a method for producing an amino acid amide derivative useful as an agricultural and horticultural fungicide.

[0002]

2. Description of the Related Art As a method for producing an amino acid amide derivative useful as an agricultural and horticultural fungicide, a method using a condensed heterocycle as an intermediate has been known. (Japanese Unexamined Patent Publication No.
176115, JP-A-8-325235)

[0003]

However, in these methods, an expensive reagent must be used as a protecting group, and the desired product can be industrially stably produced since the reaction proceeds through an unstable intermediate. Was associated with many difficulties. Thus, a method for producing an amino acid amide derivative useful as an agricultural and horticultural fungicide has been desired.

[0004]

Means for Solving the Problems The present inventors have studied an industrially advantageous method for producing an amino acid amide derivative useful as a fungicide for agricultural and horticultural use. As a result, the N-terminal was substituted with a substituted oxycarbonyl group. Using a protected dipeptide derivative as a raw material, a new method for producing an objective amino acid amide derivative by condensing and cyclizing the protected amino acid derivative with a 2-aminothiophenol derivative was found, and the present invention was completed based on this finding. .

That is, the present invention provides a compound represented by the general formula (1)

[0006]

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Wherein R ¹ is an alkyl group, a haloalkyl group, an alkenyl group, a haloalkenyl group, an alkynyl group,
A haloalkynyl group, an optionally substituted benzyl group,
Refers to a phenyl group which may be substituted, wherein R ^{2 to} R ⁵ may be the same or different, and include a hydrogen atom, an alkyl group,
A hydroxyalkyl group, a benzyl group, an optionally substituted phenyl group and a hydroxyphenylmethyl group, and X represents a hydrogen atom, an alkyl group, a haloalkyl group, an alkenyl group, an alkynyl group, an optionally substituted benzyl group, A phenyl group, a substituted imino group, a 1-benzotriazole group, an alkylcarbonyl group, a haloalkylcarbonyl group and an alkyloxycarbonyl group which may be substituted. )

A carboxyl group part of the dipeptide derivative represented by the general formula (2)

[0009]

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(Wherein Y ^{1 to} Y ⁴ may be the same or different and each represents a hydrogen atom, a halogen atom, a hydroxyl group, an alkyl group, a haloalkyl group, an alkenyl group, a haloalkenyl group, an alkynyl group, a haloalkynyl group, Group,
A haloalkoxy group, an alkenyloxy group, a haloalkenyloxy group, an alkynyloxy group, a haloalkynyloxy group, an alkylcarbonyl group, a haloalkylcarbonyl group, an alkyloxycarbonyl group, and a phenyl group which may be substituted; , Alkali metal,
1 / 2-valent alkaline earth metal, 1 / 2-valent zinc, 1/2
Valent copper, 価 -valent tin, 価 -valent iron and groups in which Y ^{1 to} Y ⁴ have the same substituents as in formula (2)

[0011]

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FIG. )

The amino group portion of the 2-aminothiophenol derivative represented by the formula (1) is condensed by a general peptide synthesis method, and without removing the intermediate product in the same reaction system, the intramolecular cyclization reaction and the By performing a subsequent self-dehydration reaction, the general formula (3)

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(In the formula, R ¹ , R ^{2 to} R ⁵ and Y ^{1 to} Y ⁴ have the same meanings as described above.)

The object of the present invention has been achieved by providing a method for producing an amino acid amide derivative useful as an agricultural and horticultural fungicide represented by the formula:

The overall reaction of the method of the present invention is represented by a series of reactions as shown in the following chemical formula (Chemical formula 9). In the chemical formula (Chemical formula 9), an intermediate product having a structure shown in parentheses is isolated. Thus, the desired amino acid amide derivative (3) can be produced in one pot without the need.

[0017]

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[0018]

DESCRIPTION OF THE PREFERRED EMBODIMENTS Terms used in the present specification will be described first.

"Alkyl" means a linear or branched aliphatic hydrocarbon having 1 to 6 carbon atoms or a cyclic aliphatic hydrocarbon having 3 to 6 carbon atoms. Specific examples include, but are not limited to, methyl, ethyl, propyl, isopropyl, cyclopropyl, normal butyl, isobutyl, tertiary butyl, cyclobutyl, pentyl, cyclopentyl, hexyl, cyclohexyl, and the like.

"Alkenyl" means one or more of the above alkyls replaced by a double bond.

"Alkynyl" means that at least one of the above alkyls and alkenyls is replaced by a triple bond.

"Alkoxy" means alkyloxy (alkyl-O-) in which the above alkyl is bonded to an oxygen atom.

"Halogen" means fluorine, chlorine, bromine and iodine.

"Haloalkyl" means one or more of the above halogens, wherein one or more of the above alkyls is substituted. "Haloalkenyl" and "haloalkynyl" are in accordance with this.

The "general peptide synthesis method" is a known method usually used for condensation of amino acids, and specifically, dehydration of a carboxyl group portion and an amino group portion by a dehydration condensing agent such as dicyclohexylcarbodiimide. Amide bond formation, ester-amino exchange formation of amide bond, reaction of acid anhydride generated in the system with amino group to form amide bond, etc., but are not limited thereto. is not.

Hereinafter, the method of the present invention will be described in detail.

In the method of the present invention, as shown in the above (Chemical formula 9), the dipeptide derivative (1) and the aminothiophenol derivative (2) are condensed to form an intermediate product, and the intermediate product S Production of an amino acid amide derivative (3) based on a reaction in which a -Q bond is cleaved under acidic conditions to form an intramolecular cyclization and a self-dehydration reaction occurs under heat or acidic conditions to form a benzothiazole ring Is the way.

The distillate used as a raw material in the method of the present invention
The peptide derivative (1) is represented by the general formula (1)
Any compound can be used.
Non-limiting examples include isopropoxycarbo
Nilvalylalanine (R¹= R^Two= Isopropyl, R^Three=
Hydrogen, R^Four= Methyl, R^Five= Hydrogen, X = hydrogen), benzyl
Oxycarbonylvalylalanine (R¹= Benzyl, R^Two
= Isopropyl, R^Three= Hydrogen, R^Four= Methyl, R^Five= Water
Hydrogen, X = hydrogen), tert-butoxycarbonylvalyl
Alanine (R¹= Tert-butyl, R^Two= Isopropi
Le, R^Three= Hydrogen, R^Four= Methyl, R^Five= Hydrogen, X = water
Element), isopropoxycarbonylphenylalanyl ara
Nin (R¹= Isopropyl, R^Two= Benzyl, R^Three= Water
Prime, R^Four= Benzyl, R^Five= Hydrogen, X = hydrogen), isopro
Poxycarbonylvalylphenylalanine (R¹= R^Two=
Isopropyl, R^Three= Hydrogen, R^Four= Methyl, R^Five= Hydrogen,
X = hydrogen), benzyloxycarbonylphenylalani
Luglycine (R¹= R^Two= Benzyl, R ^Three= R^Four= R^Five= Water
, X = hydrogen), allyloxycarbonylseryltyrosine
Unsuccinimide ester (R¹= Allyl, R^Two= Hydro
Xymethyl, R^Three= Hydrogen, R^Four= 4-hydroxybenzyl
Le, R^Five= Hydrogen, X = succinimide), 2,2-diph
Fluoroethyloxycarbonylphenylalanylphenyi
Luglycine benzyl ester (R¹= 2,2-difluo
Loethyl, R^Two= Benzyl, R^Three= Hydrogen, R^Four= Pheni
Le, R^Five= Hydrogen, X = benzyl), 4-nitrophenyl
Oxycarbonylthreonylglycine difluoromethyl
Ester (R¹= 4-nitrophenyl, R^Two= 1-hydro
Xyl, R^Three= R^Four= R^Five= Hydrogen, X = difluorome
Tyl), 3-chloropropynyloxycarbonylarani
Lulanine-1-benzotriazole ester (R¹=
3-chloropropynyl, R^Two= Methyl, R^Three= Hydrogen, R^Four
= Methyl, R ^Five= Hydrogen, X = 1-benzotriazo
), Isopropoxycarbonylvalylalanine iso
Butyloxycarboxylic anhydride (isobutyloxycal
Bonyl isopropoxycarbonylvalyl alanilate,
(R¹= Isopropyl, R^Two= Isopropyl, R^Three= Water
Prime, R^Four= Methyl, R^Five= Hydrogen, X = isobutoxycarbo
Nil)], isopropoxycarbonylvalylalaninepi
Valic anhydride (R¹= Isopropyl, R^Two= Isopropi
Le, R^Three= Hydrogen, R^Three= Methyl, R^Five= Hydrogen, X = pivalo
Yl), isopropoxycarbonylvalylalanine tri
Fluoroacetic anhydride (R ¹= Isopropyl, R^Two= Isop
Ropil, R^Three= Hydrogen, R^Four= Methyl, R^Five= Hydrogen, X = g
Trifluoroacetyl), isopropoxycarbonyl bali
Lulanine allyl ester (R¹= Isopropyl, R^Two=
Isopropyl, R^Three= Hydrogen, R^Four= Methyl, R^Five= Hydrogen,
X = allyl), isopropoxycarbonylvalylalani
Phenyl ester (R¹= Isopropyl, R^Two= Isop
Ropil, R^Three= Hydrogen, R^Four= Methyl, R^Five= Hydrogen, X =
And the dipeptide derivatives (1)
Represent the individual pure enantiomers, diastereomers and
And a mixture of them in any proportion (eg racemic, etc.)
Includes

As shown in the following scheme (Chemical Formula 10), these dipeptide derivatives (1) are, for example, amino acid derivatives (4) (formula (1)) having an N-terminal protected by an oxycarbonyl group substituted by a benzyl group or an isopropyl group. During,
R ¹ , R ² and R ³ have the same meaning as described above. ) And an amino acid derivative (5) having a carboxyl group protected by esterification (wherein R ⁴ and R ⁵ have the same meanings as described above, and R ⁶ is an alkyl group, an alkenyl group, an alkynyl group,
It represents a benzyl group which may be substituted and a phenyl group which may be substituted. ), A dipeptide ester derivative (6) (R
¹ , R ^{2 to} R ⁵ and R ⁶ have the same meaning as described above. ), The terminal ester portion of the dipeptide ester derivative (6) is further appropriately converted by a known method such as alkali saponification or catalytic reduction.

[0030]

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The amino acid derivative (4) and the amino acid derivative (5) are each known or described in, for example, “Basic and Experimental Peptide Synthesis” (Nobuo Izumiya et al.,
Maruzen Co., Ltd., 1985) p. 18, p. 26, p. 42, p. 47 and p. 50; "Peptide synthesis"
"Synthetic Chemistry Series" (Izumiya, Kato, Ohno, Aoyagi, Maruzen Co., Ltd., 1975); "Chemistry of the Amino Acids (Chemistry of the)
Amino Acids), Vol. 2, p. 891 (1
961); P. Greenstein, M .; Wi
nttz, John Wiley & Sons, N.W. Y
Publisher: "The Peptides, Volume 1, Volume 2, (1961), E. Schroede
r, K.R. Academic Pres by Luebke
s, N.R. The compound can be produced from the corresponding amino acid by a known method described in “Y.

The 2-aminothiophenol derivative (2) used as another raw material in the method of the present invention
Can be used as long as it is represented by the general formula (2). Specific examples thereof include, but are not limited to, bis (2-amino-5-fluorobenzenethiolate), -Amino-5-fluorothiophenol potassium salt, bis (2-amino-5-fluorobenzenethiolate) zinc (II), bis (2-amino-3-
Methylbenzenethiolate) zinc (II), 2-amino-4-fluorothiophenol, bis (2-amino-5
-Vinylbenzenethiolate) copper (II), bis (2-
Amino-5-methoxybenzenethiolate) iron (I
I), bis (2-amino-4-trifluoroacetylbenzenethiolate) tin (II), lithium salt of 2-amino-3-thiophenol, bis [2-amino-4- (3
-Chloropropynyl) -benzenethiolate] magnesium, calcium bis (2-amino-5-difluoromethoxybenzenethiolate) and the like.

2-aminothiophenol derivative (2)
Is known or is described, for example, in the following scheme
Or as disclosed in JP-A-6-145.
The compound can be produced from the corresponding aniline derivative according to the method described in JP-A-158.

[0034]

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In the reaction of the method of the present invention, the 2-aminothiophenol derivative (2) is used in an amount of 0.2 to 20 mol, preferably 1 to 1 mol, per 1 mol of the dipeptide derivative (1).
Used in the range of 5 moles.

The reaction of the method of the present invention is usually carried out in a solvent. The solvent that can be used here may be any solvent that does not inhibit the reaction, and specifically, hydrocarbons such as hexane, cyclohexane, benzene, and toluene; halogenated hydrocarbons such as dichloromethane, chloroform, and chlorobenzene; tetrahydrofuran; Ethers such as dioxane, dimethyl ether and methoxymethyl ether; esters such as ethyl acetate; ketones such as acetone and methyl isobutyl ketone; nitriles such as acetonitrile and propionitrile; dimethylformamide (DMF);
An aprotic polar solvent such as dimethylacetamide (DMAC) and dimethylsulfoxide (DMSO); and a mixed solvent obtained by combining solvents selected from the above can be used. The amount of the solvent used is not particularly limited, but is preferably 100 to 2 with respect to 1 mol of the dipeptide derivative (1).
0000 ml, preferably in the range of 500 to 2000 ml.

The reaction temperature in the method of the present invention is -90 ° C.
To 150 ° C, preferably -70 ° C
To 30 ° C, most preferably from -20 ° C to 5 ° C.

The reaction time may be within 48 hours, preferably in the range of 0.5 to 20 hours, most preferably 1 to 20 hours.
The range is 3 hours.

In the method of the present invention, after reacting the dipeptide derivative (1) with the aminothiophenol derivative (2) under the above conditions, the reaction system is subjected to acidic conditions (pH 2
As described above, the amino acid amide derivative (3) can be produced in one pot as described above.

[0040]

Industrial Applicability The present invention is an advantageous method for industrially easily producing amino acid amide derivatives useful as agricultural and horticultural fungicides.

[0041]

EXAMPLES The present invention will be described below in detail with reference to examples, but the present invention is not limited by these examples.

Example 1 4.1 g of N-isopropoxycarbonylvalylalanine
(0.015 mol) was dissolved in 40 ml of DMF, and 1.5 g (0.015 mol) of N-methylmorpholine was added.
2.0 g of isobutyl chlorocarbonate while stirring at -15 ° C
(0.015 mol) was slowly added dropwise so as not to exceed −10 ° C., and a mixed acid anhydride was synthesized in the system. 2.61 g (0.015 mol) of bis (5-fluoro-2-aminothiophenol) zinc salt was added thereto, and cooling was continued for 15 minutes. Thereafter, the mixture was reacted for 3 hours while slowly returning to room temperature. 5% while cooling to −15 ° C. and stirring again
Hydrochloric acid was added dropwise to adjust the pH to 2, and 200 ml of water was further added, followed by vigorous stirring to precipitate crystals. The obtained crystals were separated by filtration, washed with water, and recrystallized from a mixed solvent of water and methanol to obtain 1.9 g of N '-[1- (6-fluoro-2-benzothiazolyl) ethyl] -N-isopropoxycarbonylvalinamide ( Yield 33.3%).

Example 2 N '-[1- (6-Fluoro-2-) was prepared in the same manner as in Example 1 except that 1.8 g (0.015 mol) of pivaloyl chloride was used instead of isobutyl chlorocarbonate. [Benzothiazolyl) ethyl] -N-isopropoxycarbonylvalinamide (2.2 g, yield 38.5%) was obtained.

Example 3 1.53 g of acetic anhydride instead of isobutyl chlorocarbonate
1.9 g of N ′-[1- (6-fluoro-2-benzothiazolyl) ethyl] -N-isopropoxycarbonylvalinamide (yield 33) in the same formulation as in Example 1 except that (0.015 mol) was used. .3%).

Example 4 Acetyl chloride instead of isobutyl chlorocarbonate
Example 1 except that 17 g (0.015 mol) was used.
In the same manner as described above, 2.0 g of N '-[1- (6-fluoro-2-benzothiazolyl) ethyl] -N-isopropoxycarbonylvalinamide was obtained (yield: 35.0%).

Example 5 N '-[1- (6-Fluoro-2-) was prepared in the same manner as in Example 1 except that 3.15 g (0.015 mol) of trifluoroacetic anhydride was used instead of isobutyl chlorocarbonate.
[Benzothiazolyl) ethyl] -N-isopropoxycarbonylvalinamide (2.3 g, yield 40.2%) was obtained.

Example 6 1.2 g (0.003 mol) of N-isopropoxycarbonylvalylalanine succinimide ester and 0.63 g (0.004 mol) of zinc bis (5-fluoro-2-aminothiophenol) zinc salt in 20 ml of DMF And reacted at room temperature for 3 hours. This solution was cooled to 0 ° C., adjusted to pH 2 by adding 5% hydrochloric acid, and reacted for 0.5 hour. Further, 200 ml of water was added and the mixture was stirred vigorously to precipitate crystals. The obtained crystals were separated by filtration, washed with water, and recrystallized from a water-methanol mixed solvent to give N′-
[1- (6-Fluoro-2-benzothiazolyl) ethyl] -N-isopropoxycarbonylvalinamide
2 g (97.5% yield) was obtained.

Example 7 N-isopropoxycarbonylvalylalanine 2.74
g (0.01 mol) in 40 ml of DMF,
Ethyl-N- (3-dimethylaminopropyl) carbodiimide hydrochloride (WSC) 2.1 g (0.011 mol)
And 1.15 g of N-hydroxysuccinimide (0.01
mol) was added and reacted at room temperature for 1 hour. 2.61 g (0.015 mol) of bis (5-fluoro-2-aminothiophenol) zinc salt was added thereto, and the mixture was reacted at room temperature for 3 hours. 5% hydrochloric acid was added dropwise to adjust the pH to 2, and then water 2
Crystals were precipitated by adding 00 ml and stirring vigorously. The obtained crystals were separated by filtration, washed with water, and recrystallized from a mixed solvent of water-methanol to give 1.93 g of N '-[1- (6-fluoro-2-benzothiazolyl) ethyl] -N-isopropoxycarbonylvalinamide. (Yield 50.8
%).

Example 8 N-isopropoxycarbonylvalylalanine 2.74
g (0.01 mol) in 40 ml of DMF,
2.1 g of ethyl-N- (3-dimethylaminopropyl) carbodiimide hydrochloride (WSC) was added and stirred, and 2.61 g (0.015 mol) of bis (5-fluoro-2-aminothiophenol) zinc salt was added thereto. Was added and reacted at room temperature for 3 hours. 5% hydrochloric acid was added dropwise to adjust the pH to 2, and 200 ml of water was further added, followed by vigorous stirring to precipitate crystals. The obtained crystals were separated by filtration, washed with water, and recrystallized from a mixed solvent of water and methanol to give N '-[1- (6-fluoro-2-benzothiazolyl) ethyl] -N-isopropoxycarbonylvalinamide 1 0.8 g (yield 47.
3%).

The compounds produced by any of the examples had the same physical properties as the corresponding compounds synthesized by the method described in JP-A-8-176115.

Reference Example 1 20 g of N-isolopoxycarbonylvaline (0.098
mol) was dissolved in 40 ml of well-dried ethyl acetate, and 9.9 g (0.098 mol) of N-methylmorpholine was dissolved.
l), and the mixture was cooled to -10 ° C, and 13.5 g (0.099 mol) of isobutyl chlorocarbonate was added to -5 ° C while stirring.
The solution was dripped slowly, taking care not to exceed. After dropping the whole amount, the mixture was stirred for 5 minutes while continuing cooling. (Solution A) Alanine methyl ester hydrochloride 14
g (0.1 mol) were suspended in 30 ml of dried ethyl acetate, and cooled to 0 ° C. while N-methylmorpholine 10
g (0.1 mol) was added dropwise. After dropping the whole amount, the mixture was stirred for 1 hour while continuing to cool (solution B).

Solution B was added dropwise to solution A at -10 ° C.
After dropping the whole amount, cooling was continued for 15 minutes, and then the reaction was carried out for 4 hours while slowly returning to room temperature. 200 m of water in the reaction solution
The mixture was stirred for 10 minutes, and allowed to stand to separate an organic layer. The organic layer was washed sequentially with 1% hydrochloric acid, saturated aqueous sodium hydrogen carbonate and saturated brine, and dried over anhydrous sodium sulfate. After removing insolubles, the solvent was distilled off under reduced pressure. The obtained residue was washed with n-hexane, and recrystallized with a solvent obtained by mixing methanol and a small amount of water to give 24.5 g of N-isopropoxycarbonylvalylalanine methyl ester (yield 8).
6.2%).

Reference Example 2 N-isopropoxycarbonylvalylalanine benzyl ester (25.9 g) was prepared in the same manner as in Reference Example 1 except that alanine benzyl ester p-toluenesulfonate was used instead of alanine methyl ester hydrochloride. Rate 7
1.0%).

Reference Example 3 N-isopropoxycarbonylvalylalanine methyl ester (7.9 g, 0.027 mol) was dissolved in dimethyl sulfoxide (DMSO) (50 ml), and a 20% aqueous sodium hydroxide solution (6 ml) was added, followed by reaction at room temperature for 2 hours. . 100 ml of water was added, the pH was adjusted to 7 with dilute hydrochloric acid, and the mixture was extracted four times with 50 ml of ethyl acetate. Combine the extracts and add water 3
Washed twice with 0 ml and dried over anhydrous sodium sulfate. After removing insolubles, the extraction solvent was distilled off under reduced pressure. The obtained residue was washed with n-hexane, and recrystallized from a mixed solvent of methanol and a small amount of water to give 4.1 g of N-isopropoxycarbonylvalylalanine (yield 5).
4.7%) (mp 113-116 ° C).

Reference Example 4 11 g (0.03 mol) of N-isopropoxycarbonylvalylalanine benzyl ester was treated with 50 ml of ethyl acetate.
l, 10 g of palladium on carbon was added, and hydrogen gas was blown in at room temperature for 4 hours with stirring. The insolubles were removed and the solvent was distilled off under reduced pressure. The residue obtained is n-
The crystals were washed with hexane and recrystallized from a mixed solvent of methanol and a small amount of water to obtain 8.2 g (yield: 99%) of N-isopropoxycarbonylvalylalanine (melting point: 113 to 116 ° C).

Reference Example 5 2 g of N-isopropoxycarbonylvalylalanine
(0.0073 mol) in 20 ml of DMF.
0.72 g (0.0073 mol) of methylmorpholine
, And 1.0 g (0.0073 mol) of isobutyl chlorocarbonate was slowly added dropwise while stirring at -15 ° C so as not to exceed -10 ° C. After dropping the whole amount, the mixture was stirred for 5 minutes while continuing cooling. 0.84 g (0.0073 mol) of N-hydroxysuccinimide was added to the reaction solution.
, And the mixture was cooled and stirred for 15 minutes, and then allowed to react for 4 hours while slowly returning to room temperature. 200 ml of water, ethyl acetate 7
0 ml was added and the mixture was stirred for 10 minutes, allowed to stand, and the organic layer was separated. The organic layer was washed sequentially with 1% hydrochloric acid, saturated aqueous sodium hydrogen carbonate and saturated brine, and dried over anhydrous sodium sulfate. After removing insolubles, the solvent was distilled off under reduced pressure. The residue obtained is n-
After washing with hexane, 1.85 g (68.5% yield) of N-isopropoxycarbonylvalylalanine succinimide ester was obtained.

Claims (1)

[Claims] 1. A compound of the general formula (1) (In the formula, R ¹ represents an alkyl group, a haloalkyl group, an alkenyl group, a haloalkenyl group, an alkynyl group, haloalkynyl group, an optionally substituted benzyl group, a phenyl group which may be substituted, R ² ~ R ⁵ may be the same or different and include a hydrogen atom, an alkyl group, a hydroxyalkyl group, a benzyl group, a phenyl group which may be substituted,
X represents a hydrogen atom, an alkyl group, a haloalkyl group, an alkenyl group, an alkynyl group, an optionally substituted benzyl group, an optionally substituted phenyl group, a substituted imino group, -Represents a benzotriazole group, an alkylcarbonyl group, a haloalkylcarbonyl group and an alkyloxycarbonyl group. ) And a dipeptide derivative represented by the general formula (2): (Wherein, Y ^{1 to} Y ⁴ may be the same or different and represent a hydrogen atom, a halogen atom, a hydroxyl group, an alkyl group, a haloalkyl group, an alkenyl group, a haloalkenyl group, an alkynyl group,
Haloalkynyl group, alkoxy group, haloalkoxy group,
An alkenyloxy group, a haloalkenyloxy group, an alkynyloxy group, a haloalkynyloxy group, an alkylcarbonyl group, a haloalkylcarbonyl group, an alkyloxycarbonyl group and an optionally substituted phenyl group, and Q represents a hydrogen atom, an alkali metal, 1 / 2-valent alkaline earth metal, 1 / 2-valent zinc, 1 / 2-valent copper, 1 / 2-valent tin, 1 / 2-valent iron and Y ^{1 to} Y ⁴ are represented by the general formula (2). A group having the same substituent Is shown. By reacting with a 2-aminothiophenol derivative represented by the general formula (3): (Wherein, R ¹ , R ^{2 to} R ⁵ and Y ^{1 to} Y ⁴ have the same meanings as described above).