CS255854B2 - Process for preparing actals of alpha-sulphonyloxyketones - Google Patents

Abstract

Process for the production of α-sulfonyloxycetone acetates of formula II OR 3 OSO, -R 5 1 i 2 1 Ar-C-CH-R (II) OR4 and optionally their diastereomers, with the compound of formula V . in which 0 X II 1 i Ar - C - CH - R (V) to compounds of formula VI OR3 OH Ar - é - CH - R1 (VI) OR4 which are then reacted with the compound general formula R5 - SO2_Hal or (R5 - SC> 2) 20. The compounds of formula II represent new intermediates for alkane production acids substituted in the position aromatic group, which are useful in the pharmaceutical sector and in agriculture.

Description

The invention relates to a process for the preparation of novel compounds of formula II

OR ³ 0S0 _o -R ⁵

I ^{1 2} 1

Ar-C-CH-R

The ⁴ alpha-sulfonyloxy ketone acetals of general formula (II) wherein Ar is

a) a phenyl group which may be substituted by halogen, C ₁ _G-alkyl, C ^ _G -alkoxy, C | _G alkanoylamino, C ^ _G-haloalkyl, phenyl or oxo-2-isoindolinyl group,

(b) a naphthyl group which may be substituted by a C 1-6 alkoxy group; or

c) thienyl-, R * represents a hydrogen atom or a C 1-6 -alkyl group or Ar and R 4

R can form a fused ring with the carbon atom to which they are attached, R and R independently represent a C 1-6 alkyl group or together represent a C 2-6 -alkylene group, R 5 represents a g-alkyl group, a phenyl group which may be substituted a halogen atom or a C 1-8 -alkyl group, or a camphoryl group, and optionally diastereomers thereof.

Compounds of formula (II) are novel compounds not previously described in the literature. They represent novel intermediates which can be used as starting materials in the process for the production of alpha-substituted alkanoic acids by the aromatic group according to patents Nos. 255,851 and 255,853. Said alkanoic acids are useful in the pharmaceutical field (e.g. as anti-inflammatory agents) and in agriculture (eg as insecticides).

The process according to the invention for the preparation of the novel compounds of the above formula (II) is carried out by reacting a compound of the formula (V)

O X

Ar - C - H - R ¹ (V), wherein X represents a halogen atom and Ar and R ³ are as defined above, with an alkali metal alkoxide of the formula r ³ om, β

wherein M is an alkali metal and R is as defined above, wherein for the preparation of compounds of formula II wherein R ³ and R ⁴ have the same meaning, Ar, R ³ and R ⁵ are as defined above, the reaction of the above compound of formula V is carried out in the presence of an alcohol of formula

R ³ OH, wherein R ³ is as defined above, to give a compound of formula VI

OR OH

Ar

OR (VI) wherein R ³ and R ⁴ have the same meaning and denote a C 1-6 alkyl group. Ar and R ³ are as defined above, and for the preparation of compounds of formula II wherein R and R are different and represent a 1-alkyl group, Ar, R 4 and are as defined above, for the reaction of the above compound of formula V with said alkali metal alkoxide V2 the epoxy compound of formula VII

STEED

Ar C - CH \ /

O (VII),

Wherein Ar, R and R are as defined above, reacted with an alcohol of formula

R OH wherein R ⁴ _m have the abovementioned meaning, in the presence of an alkali metal alkoxide of the formula

R < ² >, where R < ⁴ > is as defined above and M is an alkali metal, to form a compound of general formula

41 wherein R 1 and R 2 are different and represent an O ₆ -alkyl group. Ar and R have the above ^1-4 3 4 as above, and optionally for the preparation of compounds of formula II wherein R and R 1 together represent C ₂ 5 _ ₆ -alkylene, Ar, R and R are as defined above, by reacting reacting a compound of the above formula * V with an alkylene glycol of formula

HO - R - OH wherein R is C ₂ _ ₆ -alkylene, to form a compound of formula VI, wherein R and

R ⁴ together denote C ₉ _ _T; an alkylene group. Ar and R ¹ are as defined above, and the resulting ^Zb vvi, 34 of the compound of formula VI wherein Ar and R are as defined above, R and R are independently C 1-6 alkyl or together represent C ₂ The γ-alkylene group is reacted with a compound of the general formula

R ⁵ - SO 2 - Hal or (R ⁵ - SO ₂ ) ₂ O, wherein R 1 is as defined above and Hal represents a halogen atom.

In the compounds of formulas II and V above, Ar in its broadest sense may include groups derived from cyclic compounds having aromatic character.

Thus, the groups can generally be included among the aryl groups they optionally contain

And at least one substituent and heteroaromatic groups.

a) Aryl groups, optionally containing at least one substituent

Included within the meaning of Ar are, for example, phenyl, biphenyl, and naphthyl groups.

The phenyl groups of Ar may be unsubstituted or may contain one or more substituents on the aromatic ring. Particular examples of substituents include halogen atoms such as chlorine, bromine, fluorine and iodine, alkyl groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl and tert-butyl, alkoxy groups such as methoxy, ethoxy- , n-propoxy-isopropoxy, haloalkyl groups such as trifluoroethyl and trifluoropropyl, such as heterocyclic groups oxo-isoindolinyl, alkanoylamino groups such as acetylamino and propionylamino groups.

The naphthyl groups of Ar may be substituted with alkoxy groups, preferably methoxy groups.

Preferably, 1 to 5 of said substituents, especially 1 to 3, may be attached to the aromatic ring.

Particular examples of phenyl and naphthyl groups having substituents on the aromatic ring include chlorophenyl, fluorophenyl, bromophenyl, iodophenyl, tolyl, ethylphenyl, isopropylphenyl, isobutylphenyl, tert-butylphenyl, methoxyphenyl, ethoxyphenyl, isopropoxyphenyl, trifluoroethylphenyl, oxo-isoindolinylphenyl, oxo-isoindolinylphenyl, , acetylaminobiphenyl and methoxynaphthyl.

b) Heteroaromatic groups

In the meaning of Ar, a heteroaromatic group may be a thienyl group.

The alkyl groups in said compounds of formulas II, V, VI and VII may be straight or branched chain groups. Examples of such groups include straight or branched alkyl groups having 1 to 6 carbon atoms, in particular methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, isoamyl and n-hexyl.

The alkoxy and alkanoyl groups in said compounds of formulas II, V, VI and VII have no more than 6 carbon atoms, preferably no more than 4 carbon atoms.

The alkylene groups in said compounds of formulas II and VI are preferably ethylene, propylene, butylene, trimethylene or tetramethylene.

The camphyl group R is D- or L-10-camphyl.

Various groups of compounds of formula II above are exemplified below.

Preferred aromatic groups for Ar are those of the formula R ³ -Ar ³ , wherein Ar ³ is a phenylene or naphthylene group and R ³ is a hydrogen atom, a halogen atom, a C 1-8 -alkyl group, a C 1-8 -alkoxy group, a C 1-8 -haloalkyl group , C 1-8 -alkanoylamino, oxoindolinyl, or phenyl. Another preferred example of the aromatic group Ar is thienyl.

Suitable R ³ groups are C 1-8 -alkyl groups such as methyl, ethyl, n-propyl, isopropyl or butyl. A preferred set of values for R ³ is hydrogen and C 1-8 -alkyl.

C 1-6 -alkyl groups are suitable as alkyl groups represented by R ³ and R ^{4 respectively} . As the alkylene group formed by R ³ and R ⁴ together is a suitable C ₂ _ ₁₂ ~ alkylene, such as ethylene, propylene and trimethylene.

Examples of suitable alkyl groups represented by R ³ include unsubstituted C 1-8 -alkyl groups such as methyl, ethyl, butyl, and further preferably D- or L-10-camphyl is preferred as the R ³ group. As aromatic groups R ³ , substituted or unsubstituted phenyl groups of the general formula wherein R ³ represents a hydrogen atom, a halogen atom or a C 1-6 -alkyl group are preferred.

Among the compounds of formula IX prepared by the process of the invention, those of the following compounds of formula 1-1 are preferred

Ar .2

(ί-D,

In which Ar represents a group of the formula R - Ar - or thienyl, R represents a hydrogen atom or a g-alkyl group, R ³ and R ⁴ independently represent a C 1-6 -alkyl group *

or together represent C2_i2 "alkyl ^e n ° ° for the group R represents C ^ _G-alkyl, D- or L-10-camphoryl group or a group of formula

7 and Ar, R ° and R are as defined above.

In the compound of formula (II), Ar and R1 may form a fused ring together with the carbon atom to which they are attached. A particular example of compounds of formula II in which Ar and R together form a fused ring is a compound of formula

R ^J 0,

OR ⁴

OSO ₂ -R ^a

The compounds of the formula II according to the invention can be prepared by synthesis from the alpha-haloketones of the formula V

X

Ii I i

Ar - C - CH - R (V) in which X is a halogen atom and Ar is as defined above, according to the procedure outlined in 3 in this reaction scheme:

.1

X 1 ' ¹ Ar - C - CH - R

R OM

STEED

R ³ OH OR ³ OH R ⁵ - SO ₂ - Hal 0S0 ₂ ~ R ⁵

Ar - C - CH - R ¹ or (R ⁵ SO -) - 0 Ar - C - R ¹ | δ _ ² 4->. (II)

OR (VI).

OR (VII)

In the above reaction scheme, M is an alkali metal, Hal is a halogen atom, 13 is especially chlorine, and Ar, R, R, R, R and X are as defined above.

Compounds of formula (V) may be readily prepared by treating a compound of formula (VIII)

X

AND

R-CH-COCl (VIII) -, wherein R and X are as defined above, undergoes Friedel-Crafts reaction with a compound of formula IX

Ar-H (IX), wherein Ar is as defined above, or by halogenating a compound of formula (X 0) wherein Ar and R ³ are as defined above, which is carried out in a manner known per se.

The procedure of the above reaction scheme is described in detail below.

Grade V—> VI

This step represents the effect of an alkali metal alkoxide of the formula R 4 OM on the 3 compound of the formula V in the presence of the corresponding alcohol of the formula R OH to form the alpha-hydroxyketone acetal of the formula VI. In the compound of formula (VI) produced in this step, R has the same meaning as. As alkali metal alkoxides, lithium, sodium and potassium alkoxides are expediently used. The use of sodium alkoxides is advantageous because of their low cost. The amount of alkali metal alkoxides is generally at least 1 mole per mole of the compound of formula (V). The reaction can be quenched when this compound is used in an amount of 1.5 to 3 moles per mole of the compound of formula (V). at least 1 mol per 1 mol of the compound of formula (V) may also be present. The alcohol is preferably used in excess to also serve as a solvent. It is also possible to add an aprotic solvent that is not involved in the reaction, such as diethyl ether, tetrahydrofuran, DMF or 1,2-dimethoxyethane. The reaction proceeds smoothly at a temperature in the range of -20 to about 100 ° C. To simplify the process, the reaction is preferably carried out at room temperature to 60 ° C.

Alternatively, this step may be carried out by reacting a compound of formula V with an alkali metal alkoxide 3 of formula R OM in an aprotic solvent such as diethyl ether, tetrahydrofuran or 1,2-dimethoxyethane to form an epoxy compound of formula VII which is then reacted with an alcohol of formula R @ 4 OH in the presence of a catalytic amount of an alkali metal alkoxide of the formula R ^{@ 40} M to give an alpha-hydroxyketone acetal of formula VI (see Examples 8 and 9). According to this process, a compound of formula (VI) in which R is different from R may be prepared.

The reaction of the compound of formula V with an alkali metal alkoxide of the formula R @ 4 OM can conveniently be carried out at a temperature in the range of about 0 to 60 DEG C. using 1 to 3 moles of alkali metal alkoxides per mole of the compound of formula V. with an alcohol of formula R ROH may conveniently be carried out at a temperature in the range of about 0 to 100 ° C using at least 1 mole of alcohol per mole of the compound of formula VII.

The alcohol is preferably used in excess to also serve as a solvent.

According to yet another alternative of this step, the .alpha.-haloketone of formula V in the presence of a divalent alcohol such as ethylene glycol, propylene glycol or 1,3-propanediol is reacted with a mono salt of the alcohol and an alkali metal to form an alpha-hydroxyketone acetal of formula VI. This procedure gives a product corresponding to formula VI in which and R together are alkylene ^C 2-12 'methylene, ^E, propylene or trimethylene (see Example 55).

The reaction may conveniently be carried out at a temperature of 0 to 100 ° C using at least 1 mole, preferably 1.5 to 3 mol, of an alkali metal divalent alcohol monosalts in the presence of at least 0.5 mole, preferably 2 to 10 moles, of a divalent alcohol . A non-participating aprotic solvent such as diethyl ether, tetrahydrofuran or 1,2-dimethoxyethane may be added in the reaction medium.

In the above step, the compounds of formula (VI) wherein Ar is other than phenyl or 4-chlorophenyl and the compounds of the above formula wherein R ¹ is other than hydrogen are new compounds not previously described in the literature.

Typical examples of such compounds of formula VI are given below in addition to those described in the examples: eg, a compound of formula VI wherein Ar is 2-fluoro-4-biphenylyl, R ¹ is methyl, Ar is 2-acetylamino-4-biphenylyl R 1 is methyl, Ar is 4-chlorophenyl, R 1 is isopropyl.

Stage VI- * II

This step involves the effect of the O-sulfonylating agent of the formula R-SO2. - Hal ^Z or (R 802) 2 ° ^{to the} alpha-hydroxyketone ^{acetal of} formula VI obtained in the above step to give a compound of formula II.

Examples of the O-sulfonylating agent are sulfonyl halides substituted with an aromatic group such as benzenesulfonyl chloride, p-toluenesulfonyl chloride, p-bromobenzenesulfonyl chloride, p-nitrobenzenesulfonyl chloride and naphthalenesulfonyl chloride, alkanesulfonyl halides or anhydrides of alkanesulfonic acid sulfonic acid sulfide, methanesulfonic acid sulfide. trifluoromethanesulfonyl chloride; and L- and D-10-camphorsulfonyl chloride.

The reaction is conveniently carried out under neutral to basic conditions and, in this respect, the reaction is preferably carried out in the presence of at least 1 mole of a tertiary amine such as triethylamine, pyridine or 4-dimethylaminopyridine per mole of the compound of formula VI. In this way, the reaction can be carried out at a relatively low temperature in the range of about 0 ° C to room temperature. It is also possible to add an aprotic solvent not involved in the reaction, such as methylene chloride or diethyl ether.

As described above, the compound of formula II prepared by the process of the invention can be prepared in 2 steps from the alpha-haloketone of formula V. This compound can also be produced by other methods. Such methods include oxidation of the 1-acetoxy-1-alkene substituted in the 1-position with an aromatic group of formula XI _n 3

STEED

AND

C

Ar (XI) of

Wherein Ar, R, R are as defined above to form an epoxy compound of formula VII, production of an alpha-hydroxyketone acetal of formula VI from the epoxy compound above and a further embodiment of step VI → 11, the process comprising acetalizing the corresponding alpha-sulfonyloxy ketone to a compound of formula II, and a method of reducing the alpha-oxoketone acetal of formula XII

OR ³ 0

Ar-C-CR ¹ (XII)

OR ⁴ wherein Ar, R ¹ , R ³ and Formula VI and its

R are as defined above, to form the alpha-hydroxyketone acetal of general processing in step VI → 11.

The alpha-sulfonyloxy-ketone acetal of formula (II) can also be produced by a variety of easy methods in a smaller number of steps.

The following examples illustrate the invention in detail.

Example 1

19.0 g of p-isobutylpropiophenone are dissolved in a mixture of 15 ml of anhydrous diethyl ether and ml of anhydrous dioxane and the solution is stirred at room temperature. To the solution, 17.6 g of bromine was added dropwise over 25 minutes, and the mixture was stirred for 2.5 hours. 50 ml of water are then added and the mixture is extracted three times with 20 ml of diethyl ether. The extract was washed with water (4.times.50 ml), dried over anhydrous magnesium sulphate and evaporated under reduced pressure. The residue was dissolved in 30 ml of hot methanol and cooled to -40 ° C. The precipitate was filtered off and washed with cold methanol. 21.88 g of alpha-bromo-p-isobutylpropiophenone are obtained in the form of colorless crystals. Yield 81%.

Melting point: 63-66 ° C.

IC (KBr): 2950, 1680, 1698, 1419, 1260, 1250, 1167, 955, 862 cm ^-1 .

NMR (CDCl ₃ ): δ 0.91 (6H, d, J = 7Hz), 1.87 (3H, d, J = 7Hz), 1.8-2.2 (1H, m), 52 (2H, d, J = 7Hz), 5.25 (1H, q, J = 7Hz), 7.22 (2H, d, J = 9Hz), 7.92 (2H, d, J = 9 Hz).

H, 6.37; Br, 29.69. Found: C, 57.80; H, 6.27; Br, 29.42.

Example 2

1.134 g of sodium methoxide are dissolved in 20 ml of anhydrous methanol and the solution is stirred at room temperature under an argon atmosphere. 20 ml of a solution of 2,692 g of alpha-bromo-p-isobutylpropiophenone in anhydrous methanol are added dropwise over 30 minutes at room temperature. 50 ml of water are then added to the reaction mixture and the mixture is extracted 3 times with 20 ml of diethyl ether. The extract is washed with 20 ml of water, dried over anhydrous magnesium sulfate and potassium carbonate and evaporated under reduced pressure in the presence of a small amount of potassium carbonate. 2.370 g of .alpha.-hydroxy-.beta.-isobutylpropiophenone dimethyl acetal are obtained in the form of a colorless oil.

Yield 94%. For elemental analysis, the product was purified by column chromatography (Florisil, methylene chloride).

IR (neat): 3 500, 2 950, 1 460, 1 100, 1 050, 980, 850, 800, 740 cm ^-1 ,

NMR (CDC1 _3): 0.91 (6H, d, J = 7Hz), 0.96 (3H, d, J = 7Hz), 1.6 to 2.1 (1H, m)

2.43 (2H, d, J = 7Hz), 2.57 (1H, broad s), 3.20 (3H, s), 3.30 (3H, s), 4.06 (1H, q, J = 7Hz), 7.08 (2H, d, J = 9Hz), 7.33 (2H, d, J = 9Hz).

^Analysis: Calculated: 71.39% C 9.59% H Found: 71.39% C, 9.48% H.

Example 3

9.81 g of p-toluenesulfonyl chloride are dissolved in 10 ml of anhydrous pyridine and the mixture is stirred at room temperature. 10 ml of a solution of 6.65 g of alpha-hydroxypropiophenone dimethyl acetal in anhydrous pyridine are added dropwise over 10 minutes and the mixture is stirred for 48 hours. The reaction mixture was poured onto 200 ml of ice-water and stirred for 2 hours. The resulting precipitate was filtered off, washed with water and dried under reduced pressure with potassium hydroxide. 10.91 g of alpha- (p-toluenesulfonyloxy) propiophenone dimethylacetal are obtained as colorless crystals. Yield 92%.

Melting point: 62-63 ° C (from ligroin).

IR (KBr): 1,360, 1,190, 1,175, 1,090, 1,060, 1,040, 910, 710 cm ^-1 .

NMR (CDCl ₃ ): δ 1.07 (3H, d, J = 6 Hz), 2.73 (3H, s), 3.08 (3H, s), 3.15 (3H, s) 4, 95 (1H, q, J = 6Hz), 7.33 (7H, m), 7.77 (2H, d, J = 9Hz).

Analysis for ^c 18 ^R 22 ° 5® ^! calculated: 61.70% C, 6.33% H, 9.15% S, found: 61.72% C, 6.26% H, 9.19% S.

Example 4

While cooling with ice, 26.84 g of isobutylbenzene and 29.34 g of aluminum chloride in 20 ml of carbon disulphide are stirred. 40.63 g of alpha-chloropropionyl chloride are added dropwise over 30 minutes and the mixture is stirred under ice-cooling for 1.5 hours and then for a further 30 minutes at room temperature. The reaction mixture is poured onto 200 ml of ice-water and 100 ml of concentrated hydrochloric acid are added. The mixture is extracted 4 times with 100 ml of diethyl ether. The extract was washed with 100 ml of water and then with 4 x 50 ml of saturated aqueous sodium bicarbonate solution, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The oily residue was dissolved in methanol (40 ml) at elevated temperature, treated with charcoal and cooled to -40 ° C. The precipitated crystals were filtered off, washed with cold methanol to give 17.83 g of alpha-chloro-p-isobutylpropiophenone as colorless crystals, m.p. 51-53 ° C. Yield 40%.

IR (KBr): 2950, 1690, 1 608, 1419, 1357, 1266, 1180, 956, 861 cm ^-1 .

NMR (CDCl 3: δ 0.91 (6H, d, J = 7 Hz), 1.71 (3H, d, J = 7 Hz), 1.5 to 2.2 (1H, m),

2.52 (2H, d, J = 7Hz), 5.20 (1H, q, J = 7Hz), 7.23 (2H, d, J = 9Hz), 7.91 (2H, d, J = 9Hz).

Analysis for C ^^H H^OCl:

H, 7.63; Cl, 15.78. Found: C, 69.56; H, 7.44; Cl, 15.76.

Example 5

0.979 g of sodium methoxide are dissolved in 10 ml of anhydrous methanol and the solution is stirred at room temperature under an argon atmosphere. 10 ml of a solution of 2.036 g of alpha-chloro-isobutylpropiophenone in anhydrous methanol are added dropwise over 20 minutes, and the mixture is further stirred at room temperature for 4 hours. After the usual work-up described in Example 4, 2.158 g of alpha-hydroxy-p-isobutylpropiophenone dimethylacetal is obtained in the form of a pale yellow oil. Yield 95%.

EXAMPLE 6 In a similar manner to Example 3, α-hydroxy-β-isobutyl-propiophenone dimethylacetal is prepared from dimethylacetal-α- (p-toluenesulfonyloxy) -β-isobutylpropiophenone in the form of the free; of colored crystals. Yield 89%.

Melting point: 64 to 65 ° C (from hexane).

IC (KBr): 2,960, 1,360, 1,185, 1,090, 1,050, 930, 915, 780 cm ^-1 .

NMR (CDCl ₃ ): δ 0.88 (6H, d, J = 7Hz), 1.09 (3H, d, J = 7Hz), 1.5 to 2.1 (1H, m), 40 (3H, s), 2.42 (2H, d, J = 7Hz), 3.07 (3H, s), 3.15 (3H, s), 4.93 (1H, q, J = 7Hz) )

6.9 to 7.4 (6H, m), 7.72 (2H, d, J = 9 Hz).

Analysis for ^C 22 ^H 30 O5 ^S: calculated: 64.99% C, 7.44% H, 7.89%; found: 64.78% C, 7.26% H, 7.93% S.

Example 7

2.94 g of methanesulfonyl chloride are dissolved in 5 ml of anhydrous pyridine and the solution is stirred under ice-cooling. 10 ml of a solution of 3.23 g of alpha-hydroxy-p-isobutylpropiophenone dimethyl acetal in anhydrous pyridine is added dropwise over 15 minutes. The mixture was stirred under ice-cooling for an hour and then at room temperature for 30 minutes. To the mixture was added 30 ml of water and stirred for 1 hour. The mixture was extracted 3 times with 10 ml methylene chloride, the extract was washed 3 times with 10 ml water, dried over anhydrous magnesium sulfate and evaporated in the presence of a small amount of anhydrous potassium carbonate. The oily residue was purified by column chromatography (Florisil, methylene chloride). As a colorless oil, 3.347 g of alpha- (methanesulfonyloxy) -β-isobutylpropiophenone dimethyl acetate was obtained. Yield 79%.

IR (neat): 2960, 1350, 1175, 1095, 1065, 1040, 915 cm ^-1 .

NMR (CDCl 3): δ 0.88 (6H, d, J = 7Hz), 1.16 (3H, d, J = 7Hz), 1.6-2.1 (1H, m), 2.44 (2H, d, J = 7Hz), 3.06 (3H, s), 3.18 (3H, s), 3.26 (3H, s), 4.95 (1H, q, J = 7) Hz), 7.10 (2H, d, J = 8Hz), 7.32 (2H, d, J = 8Hz).

Analysis for ^C 26 ^H I6 O5 ^S: calculated: 58.16% C, 7.93% H, 9.69%; found: 58.06% C, 7.80% H, 9.60% S.

Example 8

Sodium methoxide (9.20 g) was suspended in anhydrous diethyl ether (10 ml) and the solution stirred under ice-cooling under argon. 80 ml of a solution of 15.0 g of alpha-bromo-p-methoxypropiophenone in anhydrous diethyl ether are added dropwise over 40 minutes. After the addition was complete, the insoluble material was filtered off under argon. The filtrate was evaporated under reduced pressure to give 7.88 g (68%) of 1- (4-methoxyphenyl) -1-methoxy-1,2-epoxypropane as a pale red oil.

NMR (CDCl ₃ ): δ 1.00 <3H, d, J = 6Hz), 3.23 (3H, s), 3.52 (1H, q, J = 6Hz), 3.82 (3H, s), s) 6.92 (2H, d, J = 7Hz), 7.38 (2H, d, J = 7Hz).

Example 9

In 30 ml of anhydrous methanol, 7.88 g of 1- (4-methoxyphenyl) -1-methoxy-1,2-methoxypropane and 200 mg of sodium methoxide are stirred at room temperature for 15 hours. Water (50 ml) was added to the reaction solution, and extracted three times with 20 ml of diethyl ether. The extract was dried over anhydrous magnesium sulfate and anhydrous potassium carbonate and evaporated under reduced pressure in the presence of a small amount of anhydrous potassium carbonate. 8.26 g of alpha-hydroxy-4-methoxypropiophenone dimethylacetal are obtained as a colorless oil. For elemental analysis, this product was purified by column chromatography (Florisil, methylene chloride). Yield 61%.

IC (neat): 3,520, 1,050 cm ^-1 .

NMR (CDCl 3): δ 0.94 (3H, d, J = 7Hz), 2.35 (1H, d, J = 4Hz), 3.20 (3H, s), 3.33 (3H, s) 3.78 (3H, s), 4.05 (1H, dq, J = 7Hz), 6.18 (2H, d, J = 9Hz), 7.35 (2H, d, J =

= 9 Hz). Analysis for C- ^Hj 8 ° 4 ’ calcd, 63.70 % C, 8.02 % H found: 63.98 % C, 8.08 % H Example 10

2.67 g of p-toluenesulfonyl chloride are dissolved in 5 ml of anhydrous pyridine and the solution is stirred at room temperature. 5 ml of a solution of 1.58 g of alpha-hydroxy-p-methoxypropiophenone dimethyl acetal in anhydrous pyridine are added dropwise over 10 minutes and the mixture is stirred for 72 hours.

About 20 g of ice-water are added to the mixture and extracted 3 times with 20 ml of diethyl ether. The extracts were washed with 20 ml of water, dried over anhydrous magnesium sulphate and evaporated under reduced pressure in the presence of a small amount of anhydrous potassium carbonate. 12.12 g of alpha- (p-toluenesulfonyloxy) -p-methoxypropiophenone dimethylacetal are obtained as a pale yellow oil. Yield 80%.

IC (neat): 1,600, 1,510, 1,350, 1,245, 1,170, 1,090, 1,055, 1,035, 905 cm ^-1 .

NMR (CDCl ₃ ): δ 1.07 (3H, d, J = 7 Hz), 2.40 (3H, s), 3.07 (3H, s), 3.12 (3H, s), 3, 75 (3H, s), 4.92 (1H, q, J = 7Hz), 6.7-7.0 (2H, m), 7.1-7.4 (4H, m),

7.73 (2H, d, J = 8Hz).

Example 11

In a similar manner to Example 1, α-bromo-β- (tert-butyl) isovalerophenone was prepared as a colorless liquid from p- (tert-butyl) isovalerophenone. Yield 72%.

Boiling point: 128 to 140 ° C / 133 Pa. IR (net): 2 960, 1 680, 1600 -1 cm NMR (CDCl3) : delta 1, 00 (3H, d) J = 7 Hz), 1.20 (3 H, d, J = 7 Hz), 1.35 (9H, s); 2.7 (1H, = 10 Hz) m), 4.90 (1 H, d, , J = 9 Hz), 7.47 (2H, d, J = 10 Hz), 7.90 (2H, d, Analýza pró ^C 15 ^H 21 ^FIG vyppčteno: 60.61% C, 7.12% H, 26.89 % Br, found: 60.71% C, 7.11% H, 26.58 % Br.

Example 12

Sodium methoxide (1.62 g) was dissolved in anhydrous methanol (20 ml) and the solution was stirred at room temperature under argon. To the resulting solution was added 20 mL of a solution of 2.64 g of alpha-bromo-β- (tert-butyl) isovalerophenone in anhydrous methanol over 15 minutes, and the mixture was stirred at room temperature for 18 hours.

Conventional t-work as described in Example 2 gave 2.44 g of alpha-hydroxy-β- (tert-butyl) isovalerophenone dimethylacetal as a pale yellow oil. Yield 98%.

IR (neat): 2950, 1110, 1040 cm ^-1 .

NMR (CDCl ₃ ): δ 0.70 (3H, d, J = 7Hz), 0.90 (3H, d, J = 7Hz), 2.32 (9H, s), 1.0 to

1.6 (1H, m), 2.45 (1H, broad s), 3.22 (3H, s), 3.25 (3H, s), 3.67 (1H, d, J = 6 Hz) ), 7.33 (4H, s).

Example 13

1.90 g of methanesulfonyl chloride are dissolved in 5 ml of anhydrous pyridine and the solution is stirred at room temperature. 5 ml of a solution of 2.34 g of alpha-hydroxy-β- (tert-butyl) isovalerophenone dimethyl acetal in anhydrous pyridine are added dropwise over 10 minutes and the mixture is stirred at this temperature for a further 24 hours. Conventional work-up and separation of the product as described in Example 7 afforded 1.63 g of alpha- (methanesulfonyloxy) -β- (tert-butyl) isovalero phenone dimethylacetal which forms a colorless oil (crystallizing upon standing at room temperature). Yield 55%.

Melting point: 80-86 ° C.

IR (neat): 2960, 1357, 1176, 1060, 955 cm ^-1 NMR (CDC1 _3): delta 0.70 (3H, d, J = 7Hz), 0.90 (3H, d, J = 7 Hz), 1.32 (9H, s), 1.4 to 9 Hz

1.9 (1H, m), 3.17 (3H, s), 3.20 (3H, s), 3.26 (3H, s), 4.76 (1H, d, J = 4Hz), 7.37 (4 H, s).

Analysis for ^C 30 ^H I8 ° ^{to 5:} calculated: 60.30% C, 8.44% H, 8.95%; found: 60.07% C, 8.33% H, 9.07% S.

Example 14

To a mixture of 7.12 g of alpha-acetoxyacetophenone, 7.44 g of ethylene glycol and 0.200 g of p-toluenesulfonic acid monohydrate was added 100 ml of benzene, and the mixture was heated to reflux. The resulting water is removed with a Dean-Stark attachment attached to the reaction vessel.

After 21 hours at reflux, 4.00 g of ethylene glycol are added. The mixture was further refluxed for 6 hours. The resulting water is distilled off. After cooling, 30 ml of saturated aqueous sodium bicarbonate solution and 20 ml of water are added successively to the mixture, and the mixture is extracted twice with 30 ml of diethyl ether. The extracts were washed with 10 ml of water, dried over anhydrous magnesium sulphate and evaporated under reduced pressure. 7.874 g of a residue are obtained, which according to NMR and gas-liquid chromatography consists of a mixture of alpha-hydroxyacetophenone ethylene acetate and alpha-acetoxyacetophenone ethylene acetal. The mixture was dissolved in 20 ml of methanol and 0.300 g of potassium carbonate was added. The mixture was stirred at room temperature for 4 hours, water (200 ml) was added and the colorless crystalline precipitate was filtered and dried under reduced pressure with potassium hydroxide overnight. 4.79 g of .alpha.-hydroxyacetophenone ethylene acetal are obtained. Yield 67%;

NMR (CDCl 3): δ 2.10 (1H, broad s), 3.70 (2H, broad s), 3.7 to 4.0 (2H, m), 4.0 to 4.2 (2H, m 7.2-7.6 (5H, m).

Example 15

To 0.900 g of alpha-hydroxyacetophenone ethylene acetal was added 5 ml of pyridine and the mixture was stirred under ice-cooling. 1.08 g of p-toluenesulfonyl chloride was added to the mixture, stirred for 2 hours under ice-cooling and then for 1 hour at room temperature. The reaction mixture was ice-cooled, water (10 ml) was added and the mixture was stirred for 1 hour and extracted with diethyl ether (3 x 20 ml). The extracts were washed twice with 10 ml of water, dried over anhydrous magnesium sulphate and evaporated under reduced pressure. 1.584 g of a crystalline residue is obtained, which is washed with a small amount of hexane to give 1.330 g of alpha (p-toluenesulfonyloxy) acetophenone ethylene acetal as colorless crystals. Yield 80%.

NMR (CDCl ₃ ): δ 2.40 (3H, s), 3.7-3.9 (2H, m), 3.9-4.1 (2H, m), 4.11 (2H, s) ,

7.1 to 7.5 (5H, m), 7.55 (2H, d, J = 8Hz).

Example 16

Following a similar procedure to that of Example 15, alpha- (p-bromobenzenesulfonyloxy) acetophenone ethylene acetal is obtained as colorless crystals from alpha-hydroxyacetophenone ethylene acetal. Yield 86%.

NMR (CDCl ₃ ): δ 3.7-3.9 (2H, m), 3.9-4.1 (2H, m), 4.16 (2H, s), 7.2-7.5 ( 5H, m), 7.63 (4H, s).

Example 17

0.46 g of sodium metal was dissolved in 10 ml of anhydrous methanol and the solution was stirred at room temperature. 10 ml of a solution of 2.19 g of 1- (2-thienyl) -2-bromo-1-oxopropane in anhydrous methanol are added dropwise over 10 minutes, and the mixture is stirred at room temperature for 3.5 hours. The usual work-up as in Example 2 gave 1.900 g of 1- (2-thienyl) -2-hydroxy-1-oxopropane dimethylacetal as a colorless oil. Yield 94%.

IC (neat): 3,450, 1,110, 1,055, 980, 855, 710 cm ^-1 .

NMR (CDCl ₃ ): δ 1.05 (3H, d, J = 7 Hz), 2.54 (1H, broad s), 3.26 (3H, s), 3.30 (3H, s),

4.16 (1H, broad q, J = 7 Hz), 6.9-7.2 (2H, m), 7.2-7.4 (1H, m).

Example 18

0.606 g of 1- (2-thienyl) -2-hydroxy-1-oxopropane dimethylacetal is dissolved in 5 ml of pyridine and the solution is stirred under ice-cooling. To the solution, 0.30 mL of methanesulfonyl chloride was added over 1 minute, and the mixture was stirred under ice-cooling for 5 minutes and then at room temperature for 5 hours.

To the mixture was added 30 ml of water and stirred at room temperature for 30 minutes. It is then extracted 3 times with diethyl ether. The extracts were washed twice with 10 ml of water, dried over anhydrous magnesium sulfate and anhydrous potassium carbonate, and evaporated under reduced pressure. The residue was purified by column chromatography (Florisil, methylene chloride). 0.788 g of 1- (2-thienyl) -2- (methanesulfonyloxy) -1-oxopropane dimethylacetal was obtained as a colorless oil. Yield 94%.

IR (neat): 1,360, 1,180, 1,120, 1,055, 990, 975, 930, 905, 855, 810, 715, 540, 525 cm ^-1 .

NMR (CDCl ₃ ): δ 1.27 (3H, d, J = 7Hz), 3.09 (3H, s), 3.27 (6H, s), 5.02 (1H, q, J = 7) Hz),

6.9 to 7.1 (2H, m), 7.2 to 7.4 (1H, m).

H, 5.75; S, 22.87. Found: C, 42.64; H, 5.64; S, 22.90.

Example 19

2.01 g of benzenesulfonyl chloride are dissolved in 10 ml of anhydrous pyridine and the solution is stirred at room temperature. 10 ml of a solution of 1.93 g of .alpha.-hydroxy-p-isobutylpropiophenone dimethylacetal in anhydrous pyridine are added dropwise over 15 minutes and the mixture is stirred for 72 hours. »By treatment similar to Example 3, 2.62 g of dimethylacetal are obtained as colorless crystals. alpha (benzenesulfonyloxy) -β-isobutylpropiophenone. Yield 88%.

Melting point: 79-82 ° C.

iC (KBr): 2 950, 1 362, 1 195, 1,097, 1,043, 990, 921, 813, 594 cm ^-1 . NMR (CDC1 _3): : delta 0.86 I (6H, d. J = 7Hz), 1.08 (3H, d, J = 7 Hz), 1.6 to 2.1 (1 H, m), 2.41 (2H, d, J = 7 Hz), 3.02 (3H, s), 3.10 (3H, s) 4.94 (1H,  q, J 7 Hz), 7.04 (2H, d, J = 9 Hz), 7.19 (2H, d, J = 9) Hz), 7.36 to 7 , 70 (3H, m), 7.84-7 8.02 (2H, m).

Example 20

1.91 g of p-toluenesulfonyl chloride are dissolved in 10 ml of anhydrous pyridine and the solution is stirred at room temperature. 10 ml of a solution of 1.13 g of alpha-hydroxypropiophenone diethyl acetal in anhydrous pyridine are added dropwise over 10 minutes and the mixture is stirred for 72 hours. The usual work-up and purification by column chromatography gave 1.16 g of alpha- (p-toluenesulfonyloxy) propiophenone diethyl acetal as a colorless oil. Yield 85%.

IR (neat): 2,980, 1,360, 1,192, 1,178, 1,087, 1,055, 1,042, 920 cm ^-1 .

NMR (CDCl ₃ ): δ 0.8-1.3 (9H, m), 2.38 (3H, s), 3.1-3.6 (4H, ra), 4.89 (1H, q, J = 7 Hz), 7.1 to 7.5 (7H, m), 7.80 (2H, d, J = 9 Hz).

Analysis for ^C 20 ^H 26 O5 ^S:

calculated: 63.46% C, 6.93% H, 8.47% N found: 63.54 l C, 6.90% H, 8.35% N Example 21

In a similar manner to Example 17, 1- (4-methoxyphenyl) -2-hydroxy-1-oxopropane dimethylacetal was prepared as a light yellow oil from 1- (4-methoxyphenyl) -2-bromo-1-oxopropane. Without further purification, the crude product was used in the reaction of Example 22.

Example 22

In a similar manner to Example 7, 1- (4-methoxyphenyl) -2-methanesulfonyloxy-1-oxopropane dimethylacetal was obtained as pale yellow from 1- (4-methoxyphenyl) -2-hydroxy-1-oxopropane dimethylacetal (obtained in Example 21). oils. The yield is 80.1% (calculated on 1- (4-methoxyphenyl) -2-bromo-1-oxopropane).

IR (neat): 2,935, 1,615, 1,517, 1,358, 1,257, 1,176, 1,100, 1,065, 145, 915 cm ^-1 .

NMR (CDCl ₃ ): δ 1.18 (3H, d, J = 6 Hz), 3.09 (3H, s), 3.21 (3H, s), 3.28 (3H, s) 3.80 (3H, s), 4.97 (1H, q, J = 6Hz), 6.87 (2H, d, J = 9Hz), 7.37 (2H, d, J = 9Hz).

Example 23

In a similar manner to Example 20, 1- (2-thienyl) -2- (p-toluenesulfonyloxy) -1-oxopropane dimethylacetal was prepared from 1- (2-thienyl) -2-hydroxy-1-oxopropane dimethylacetal in the form of colorless oil. Yield 64%.

IR (neat): 1,360, 1,190, 1,180, 1,060, 985, 925, 905, 820, 790, 710, 665, 565 cm ^-1 .

NMR (CDCl ₃ ): δ 1.19 (3H, d, J = 7 Hz), 2.40 (3H, s), 3.08 (3H, s), 3.14 (3H, s), 4, 98 (1H, q, J = 7Hz), 6.94 (2H, d, J = 3Hz), 7.2 to 7.4 (3H, m), 7.80 (2H, d, J = 8 Hz).

Example 24

In a similar manner to Example 20, 1- (2-thienyl) -2-hydroxy-1-oxopropane dimethylacetal and benzenesulfonyl chloride was prepared as 1- (2-thienyl) -2-benzenesulfonyloxy-1-oxopropane dimethylacetal as a colorless oil. The yield is 83%.

IR (net) : 1,360, 1,190, 1,060, 980, 925, 900, 590, 555 cm 1. NMR (CDCl3 ₎ ): delta 1.20 (3H, d, J = 7Hz), 3.08 (3H, s) 3.14 (3H, s), 5.01 (1H, q, J = 7) 6.8 to 7.1 (2H, m), 7.2 to 7.4 (1H, m), 7.4 to 7.7 (3H, m) 7.9 to 8.1 (2H, ni) Example 1 and d 25 At 30 Dissolve ml of anhydrous ethanol 1.30 g (56.5 nunol) of sodium metal and the mixture is stirred stirring at room temperature. Within 15 minutes se k solution dropwise 20 ml of the 5.33 g solution

(0.025 mol) alpha-bromopropiophenone in anhydrous ethanol and the mixture was further stirred at room temperature for 40 minutes. 100 ml of water are then added and the mixture is extracted twice with 60 ml of diethyl ether. The extracts were washed with water, dried over anhydrous magnesium sulfate and anhydrous potassium carbonate and evaporated under reduced pressure. The residue was dissolved in 30 ml of anhydrous ethanol containing a catalytic amount of sodium metal dissolved therein and the solution was stirred at room temperature for 2 days. The usual work-up as in Example 2 gave 4.497 g of 1-phenyl-2-hydroxy-1-oxopropane diethyl acetal as a colorless oil. Yield 80.2%.

IC (neat): 2,960, 1,452, 1,120, 1,092, 1,057, 1,040, 772, 709 cm ^-1 .

NMR (CDCl 3): δ 0.94 (3H, d, J = 6 Hz), 1.05-1.40 (6H, m), 2.61 (1H, broad s), 3.22-3. 83 (4H, m), 4.05 (1H, q, J = 6 Hz), 7.1-7.7 (5H, m).

Example 26

3.33 g of acetanilide and 4.0 ml (5.2 g) of alpha-chloropropionyl chloride are stirred at room temperature in 20 ml of carbon disulfide. Then, 7.0 g of aluminum chloride as a fine powder was added to the solution over 2 minutes. The mixture was stirred at room temperature for 25 minutes and refluxed with stirring for 50 minutes. After cooling, the reaction mixture was divided into 2 layers. The upper layer was removed by decantation and the lower layer was black and tar-like and poured onto ice-water. The precipitated crystals are filtered off. Recrystallization from ethanol to give 1.860 g of 1- (4-acetylaminophenyl) -2-chloro-1-oxopropane as colorless crystals. The upper layer of the reaction mixture, the crystal collected filtrate and the mother liquor from the recrystallization were combined and extracted three times with 50 ml of methylene chloride. The extracts were washed with 50 ml of water, dried over anhydrous magnesium sulphate and evaporated under reduced pressure. Recrystallization of the residue from ethanol gave 1.434 g of 1- (4-acetylaminophenyl) -2-chloro-1-oxopropane. The mother liquors were evaporated under reduced pressure and the residue was purified by column chromatography (silica gel, methylene chloride and ether). Recrystallization from methanol further affords 0.868 g of the above product. Thus, the total amount of product is 4.162 g and the overall yield is 75%. The substance forms colorless crystals.

Melting point: 123-125 ° C (from ethanol).

XC (KBr): 1690, 1675, 1595, 1540, 1415, 1320, 1360, 1180, 965, 860, 665 cm ^-1 .

NMR (CDCl ₃ ): δ 1.70 (3H, <5, J = 7Hz) 2.18 (3H, s), 5.18 (1H, q, J = 7Hz), 7.63 (2H, d, J = 9 Hz), 7.95 (2H, d, J = 9 Hz), 7.8-8.1 (1H, broad s).

Analysis for C ^^ H ^ ₂ ^ε 1 ^{ΝΟ 2:} calculated: 58.54% C, 5.36% H, 15.71% Cl 6.21% N Found: 58.59% C, 5.40 % H, 15.63% Cl, 6.23% N.

Example 27

In a similar manner to Example 17, 1- (4-acetylaminophenyl) -2-hydroxy-1-oxopropane dimethylacetal was prepared as a glassy substance from 1- (4-acetylaminophenyl) -2-chloro-1-oxopropane. The crude product was used without purification in the reaction of Example 28.

NMR (CDCl ₃ ): δ 0.95 (3H, d, J = 7 Hz) 2.14 (3H, s), 2.94 (1H, broad s), 3.21 (3H, s),

3.33 (3H, s), 4.10 (1H, q, J = 7Hz), 7.37 (2H, d, J = 8Hz), 7.51 (2H, d, J =

Hz), 8.93 (1H, broad s).

Example 28

All of the 1- (4-acetylaminophenyl) -2-hydroxy-1-oxopropane dimethylacetal obtained in the example was dissolved in 5 ml of pyridine and 0.60 ml (0.89 g) of methanesulfonyl chloride was added. After stirring at room temperature for 5 hours, the reaction mixture was cooled with ice and 30 ml of water were added. The temperature is allowed to return to room temperature, the mixture is stirred for 10 minutes and then extracted 4 times with 20 ml of ethyl acetate. The extracts were dried by successive addition of anhydrous sodium sulfate and anhydrous magnesium sulfate, and evaporated under reduced pressure. The residue was purified by column chromatography (Florisil, methylene chloride and diethyl ether) to give 1.537 g of 1- (4-acetylaminophenyl) -2-methanesulfonyloxy-1-oxopropane dimethylacetal as a colorless glassy substance. The yield is 93% (calculated on 1- (4-acetylaminophenyl) -2-chloro-1-oxopropane).

IR (KBr): 1675, 1610, 1540, 1350, 1175, 915, 525 cm ^-1 .

NMR (CDCl 3): δ 1.14 (3H, d, J = 7 Hz), 2.52 (3H, s), 3.08 (3H, s), 3.18 (3H, s), 3.24 (3H, s), 4.94 (1H, q, J = 7Hz), 7.36 (2H, d, J = 9Hz), 7.54 (2H, d, J = 9Hz), 8, 52 (1H, broad s).

Example 29

In the same manner as in Example 17, 1- (4-fluorophenyl) -2-bromo-1-oxopropane was prepared from 1- (4-fluorophenyl) -2-hydroxy-1-oxopropane dimethylacetal as a pale yellow oil. Without purification, this product was used in the reactions of Examples 25 and 31.

IR (neat): 2,975, 2,937, 1610, 1512, 1230, 1159, 1 105, 1053, 982, 839 cm ^-1 .

NMR (CDCl 3): δ 0.93 (3H, d, J = 6 Hz), 2.53 (1H, broad s), 3.23 (3H, s), 3.33 (3H, s), 4, Δ (1H, broad q, J = 6 Hz), -6.83 to 7.18 (2H, m), 7.32 to 7.60 (2H, m).

Example 30

In the same manner as in Example 7, 1- (4-fluorophenyl) -2-methanesulfonyloxy-1-oxopropane dimethylacetal (obtained in Example 29) was prepared in the form of colorless oils. The yield was 82.3% (calculated on 1- (4-fluorophenyl) -2-bromo-1-oxopropane).

IC (neat): 2,940, 1,610, 1,512, 1,359, 1,228, 1,180, 1,160, 1,098, 1,067, 1,045, 972,

918 cm ^'3'.

NMR (CDCl ₃ ): δ 1.15 (3H, d, J = 6 Hz), 3.06 (3H, s), 3.21 (3H, s), 3.24 (3H, s), 4, 96 (1H, q, J = 6Hz), 6.88-7.16 (2H, m), 7.32-7.58 (2H, m).

Example 31

In the same manner as in Example 20, 1- (4-fluorophenyl) -2- (p-toluenesulfonyloxy) -1- (dimethylacetal) dimethylacetal was prepared from 1- (4-fluorophenyl) -2-hydroxy-1-oxopropane dimethylacetal (obtained in Example 29). 96 DEG-99 DEG C. oxopropane as colorless crystals. The yield is 76.2% (calculated on 1- (4-fluorophenyl) -2-bromo-1-oxopropane).

Melting point: 101 ° C (from methanol).

IC (KBr): 2 948, 1 605, 1 510, 1 360, 1 346, 1 192, 1 181, 1 090, 1 053, 932, 918, 820, 786, 670, 561 cm ^-1 .

NMR (CDCl ₃ ): δ 1.05 (3H, d, J = 6 Hz), 2.40 (3H, s), 3.08 (3H, s), 3.10 (3H, s), 4, 93 (1H, q, J = 6Hz), 6.82-7.08 (2H, m), 7.16-7.46 (4H, m), 7.73 (2H, d,

J = 8Hz).

Analysis for ^C g ^H 2] ^FO 3 ^S: Calculated: C 58.68%, H 5.75 and Found: C, 58.98 i 5.96 i H.

Example 32

8.57 g of 1- (6-methoxy-2-naphthyl) -1-oxopropane (U.S. Pat. No. 2,683,738) are dissolved in 60 ml of anhydrous dioxane and the solution is stirred at room temperature. To the solution was added 13.57 g of pyridinium hydrobromide perbromide and then stirred for an additional hour. 200 ml was added to the mixture

3% aqueous sodium bisulfite solution and after stirring at room temperature for 3 hours, the precipitated crystals are filtered off, washed with water and dried under reduced pressure with potassium hydroxide. 11.66 g of 1- (6-methoxy-2-naphthyl) -2-bromo-1-oxopropane are obtained in the form of pale yellow crystals and a melting point of 73-75 ° C. Yield 99%.

Melting point: 68 to 69 ° C (from benzene).

NMR (CDCl 3: δ 1.90 (3H, d, J = 7Hz), 3.85 (3H, s), 5.36 (1H, q, J = 7Hz), 6.9-7.3 ( 2H, m), 7.5-8.1 (3H, m), 8.38 (1H, broad s).

Analysis for C ^^ H ^^ BrO ^:

calculated: 57.35% C, 4.47% H, 27.26% Br, found: 57.27% C, 4.66% H, 27.23% Br.

Example 33

In a similar manner to Example 2, 1- (6-methoxy-2-naphthyl) -2-hydroxy-1-oxopropane dimethylacetal was prepared from 1- (6-methoxy-2-naphthyl) -2-bromo-1-oxopropane in the form of colorless oil. Yield 100%. The product crystallized after purification by column chromatography (Florisil, methylene chloride) and on standing at room temperature. The substance forms colorless crystals.

Mp 56-59 ° C.

IC (KBr): 3500, 1637. 1,610, 1,488, 1,276, 1,215, 1,175, 1,118, 1,106, 1,040, 859 cm ^-1 .

NMR (CDCl 3): δ 0.97 (3H, d, J = 7 Hz), 2.48 (1H, broad s), 3.20 (3H, s), 3.36 (3H, s),

3.82 (3H, s), 4.14 (1H, q, J = 7Hz) 7.00 to 7.24 (2H, m), 7.40 to 7.98 (4H, m).

Analysis for ^c 16 ^H 20 ° 4 ^: calculated: 69.54% C, 7.30 % H found: 69.25% C, 7.28 % H Example 34

In a similar manner to Example 7, 1- (6-methoxy-2-naphthyl) -2-methanesulfonyloxy-1-oxopropane dimethylacetal was prepared from 1- (6-methoxy-2-naphthyl) -2-hydroxy-1-oxopropane dimethylacetal in in the form of a colorless oil. Yield 84%.

IC (neat): 1,640, 1,615, 1,492, 1,360, 1,280, 1,182, 901, 820 cm ^-1 .

NMR (CDCl 3) δ 1.19 (3H, d, (1H, q, J = 7 Hz),

J = 7 Hz), 3.09 (3H, s), 3.22 (3H, s), 3.31 (3H, s), 3.87 (3H, s), 5.05 7.04 to 7 24 (2H, m), 7.42-7.94 (4H, m).

Analysis calculated for:

C 57.61, H 6.26, C 57.21, H 6.02,

Example

S 9.05%, S 8.85%.

350 mg of sodium metal was dissolved in 40 ml of anhydrous methanol and the solution was stirred at room temperature. To the solution was added 2.93 g of 1- (6-methoxy-2-naphthyl) -2-bromo-1-oxopropane, and then stirred for 24 hours. The mixture is mixed with 50 ml of water and then extracted 4 times with 15 ml of methylene chloride each time. The extract was dried over anhydrous magnesium sulfate and anhydrous potassium carbonate and evaporated under reduced pressure. 2.845 g of crude 1- (6-methoxy-2-naphthyl) -2-hydroxy-1-oxopropane dimethyl acetal are obtained; 1.11 g of the crude product was dissolved in 3 ml of anhydrous pyridine and then stirred at room temperature. To the solution was added 993 mg of D-10-camphorsulfonyl chloride and the mixture was stirred for 40 minutes. 20 ml of water are added to the mixture and then extracted 3 times with 10 ml of methylene chloride. The extract was dried by successive addition of anhydrous magnesium sulfate and anhydrous potassium carbonate, and then evaporated under reduced pressure. The remaining oil was purified by column chromatography (Florisil, methylene chloride) to give 1.477 g of 1- (6-methoxy-2-naphthyl) -2- (D-10-camphorsulfonyloxy) -1-oxopropane dimethylacetal as a glass-like colorless substance. The yield is 76.8% (calculated on 1- (6-methoxy-2-naphthyl) -2-bromo-1-oxopropane). The product is a 1: 1 mixture of two diastereomers as determined by high performance liquid chromatography and by NMR spectrum.

1.067 g of the product thus obtained are dissolved in 4 ml of methanol and the solution is allowed to stand at 2-4 DEG C. for days. 355 mg of colorless crystals with a melting point of 90-95 ° C are obtained. The crystals were further recrystallized from methanol to give 220 mg of one of the diastereomers as pure product.

Melting point: 102-105 ° C.

[.alpha.] D @ 25 = + 32.5 DEG (c = 1, chloroform).

IR (KBr): 2,950, 1,753, 1,634, 1,611, 1,487, 1,354, 1,273, 1,219, 1,180, 1,166, 1,068,

042, 990, 919, 899, 862, 840 cm ^-1 .

NMR (CDCl ₃ ): δ 0.87 (3H, s), 1.12 (3H, s), 1.23 (3H, d, J = 6 Hz), 1.3-2.7 (7H, m ), 3.04 (1H, d, J = 15Hz), 3.24 (3H, s), 3.35 (3H, s), 3.86 (3H, s), 3.86 (1H, d) , J = 15Hz),

5.15 (1H, q, J = 6Hz), 7.04-7.26 (2H, m), 7.46-7.98 (4H, m).

Analysis ^ 26 ^ 33 ^ ¹ ^^ 7: calculated: 63.78% C, 6.79% H, 6.55%; found: 63.66% C, 7.06% H, 6.57% S .

The second diastereomer is separated from the mixture as a colorless oil by high performance liquid

chromatography (column: Microporasil, column size: 7.8 mm x 30 cm, unwinding solvent- (hexane: ethyl acetate 9: 1). [.Alpha.] D @ ²⁵ = + 4.2 DEG (c = 0.143, chloroform) • IR (KBr): 2,950, 1,750, 1,631, 1,608, 1,485, 1,352, 1,271 , 1,216, 1,172, 1,062, 1 040 985 914, 895, 855, 810 cm ¹ . NMR (CDCl ₃ ): δ 0.91 (3H, s), 1.14 (3H, s), 1.26 (3H, d, J = 6 Hz), 1.3 to 2.7 (7H, m) 3.29 (1H, d, J = 15Hz); 3.30 (3H, s), 3.42 (3H, s), 3.74 (1 H, d, J = = 15 Hz)

3.96 (3H, s), 5.20 (1H, q, J = 6Hz), 7.10 to 7.30 (2H, m), 7.50 to 8.02 (4H, m)

Example 36

In a similar manner to Example 17, 1- (4-chlorophenyl) -2-hydroxy-1-oxopropane dimethylacetal was prepared as a colorless oil from 1- (4-chlorophenyl) -2-bromo-1-oxopropane. This product was used in the reaction of Example 37 without further purification.

IR (neat): 3 450, 2 975, 2 930, 1 600, 1 492, 1 398, 1 108, 1 095, 1 052, 1 016, 980, 829, 743 cm -1.

Example 37

In the same manner as in Example 20, 1- (4-chlorophenyl) -2- (p-toluenesulfonyloxy) -1-oxopropane dimethylacetal was prepared from the 1- (4-chlorophenyl) -2-hydroxy-1-oxopropane dimethylacetal obtained in Example 36 in 76 DEG-77 DEG. Yield 86% (calculated on 1- (4-chlorophenyl) -2-bromo-1-oxopropane).

Melting point: 78 to 79 ° C (from methanol).

iC (KBr): 2,945, 1,501, 1,493, 1364, 1,347, 1,195, 1,188, 1,094, 1,057, 1,110, 936, 919,

822, 789, 669, 565 cm ¹ .

NMR (CDCl ₃ ): δ 1.05 (3H, d, J = 6 Hz) 2.40 (3H, s), 3.08 (3H, s), 3.10 (3H, s), 4.93 (1H, q, J = 6Hz), 7.25 (4H, s), 7.27 (2H, d, J = 8Hz), 7.76 (2H, d, J = 8Hz).

Analysis for ^C 21 ^H ig ^S ° 3 ^{G ^:} Calculated: 56.17% C, 5.50% H, 9.21% Cl, 8.33%; found: 56.22% C, 5.48% H, 9.13% Cl, 8.32% S.

Example 38

In the same manner as in Example 26, 1- (4-) -1-oxo-6-isoindolinyl (phenyl) -2-chloro-1-oxopropane was prepared as colorless crystals from 2-phenyl-1-isoindoline and alpha-chloropropionyl chloride. Yield 89%.

Example 39

In the same manner as in Example 17, 1- (4-) - 2-oxo-2-isoindolinyl (phenyl) -2-chloro-1-oxopropane was prepared from 1- (4-) 1-oxo-2-isoindolinyl (phenyl) dimethyl acetal 2-hydroxy-1-oxopropane as colorless crystals, m.p. 130-135 ° C. The yield is 83%.

IC (KBr): 3530, 1680, 1515, 1385, 1310, 1120, 1045, 740 cm ^-1 .

NMR (CDCl 3): δ 0.96 (3H, d, J = 7 Hz), 2.36 (1H, broad s), 3.20 (3H, s), 3.33 (3H, s), 4, 10 (1H, broad q, J = 7Hz), 4.80 (2H, s), 7.4-7.6 (5H, m), 7.8-8.0 (3H, m).

Analysis for iW calcd, 69.70 % c, 6.47% H, N, 4.28 found: 69.63 % c, 6.49% H, N, 4.21 Example 40

In the same manner as in Example 28, 1- (4-) 1-oxo-2-isoindolinyl (phenyl) -2-hydroxy-1-oxopropane and methanesulfonyl chloride dimethylacetal gave 1- (4-) 1-oxo-2-isoindolinyl dimethylacetal (phenyl) -2-methanesulfonyloxy-1-oxopropane as colorless crystals, yield 95%.

IC (KBr): 1695, 1520, 1390, 1350, 1340, 1175, 975, 910, 740 cm ^first

NMR (CDCl ₃ ): δ 1.20 (3H, d, J = 7 Hz), 3.11 (3H, s), 3.24 (3H, s), 3.30 (3H, s), 4, 81 (2H, s), 5.00 (1H, q, J = 7Hz), 7.4-7.6 (5H, m), 7.8-8.0 (3H, m).

Example 41

In the same manner as in Example 17, 1- (4-biphenylyl) -2-hydroxy-1-oxopropane dimethylacetal was prepared as colorless crystals from 1- (4-biphenylyl) -2-bromo-1-oxopropane as colorless crystals, m.p. 78.5. to 80 ° C. Yield 95%.

Melting point: 78.5 to 80 ° C (from ether and n-hexane).

NMR (CDCl 3): δ 1.00 (3H, d, J = 7Hz), 2.44 (1H, d, J = 3.1Hz), 3.23 (3H, s), 3.37 (3H) s), 4.12 (1H, q, d, J = 7Hz, 3.1Hz), 7.2-7.7 and 7.55 (mass, 9H).

IR (KBr): 1 118, 1 102, 1 045, 1 007, 979, 838, 770, 735, 695 cm ^-1 .

H, 7.40%. Found: C, 74.88; H, 7.27.

Example 42

In the same manner as in Example 7, 1- (4-biphenylyl) -2-hydroxy-1-oxopropane dimethylacetal was prepared as 1- (4-biphenylyl) -2-methanesulfonyloxy-1-oxopropane dimethylacetal as a colorless oil.

IR (neat): 1,490, 1,357, 1,335, 1,177, 1,1 123, 1,100, 1,065, 1,045, 971, 916, 847, 811, 773, 753, 740, 702, 538, 527 cm ^-1 .

NMR (CDCl 3): δ 1.21 (3H, d, J = 7 Hz), 3.03 (3H, s), 3.24 (3H, s), 3.31 (3H, s), 5.01 (1H, q, J = 7 Hz) 7.1-7.7 (rrt), up to 7.56 (s) all 9H.

Example 43

In a similar manner to that described in Example 17, 1,1-dimethoxy-2-hydroxy-1,2,3,4-tetrahydronaphthalene was prepared from 2-bromo-1-oxo-1,2,3,4-tetrahydronaphthalene. Without purification, this product was used in the reaction of Example 44.

IR (neat): 1138, 1080, 1058, 767 cm ^1st

Example 44

In a similar manner to Example 7, 1,1-dimethoxy-2-methanesulfonyloxy-1,2,3,4- was prepared from the 1,1-dimethoxy-2-hydroxy-1,2,3,4-tetrahydronaphthalene obtained in Example 43. tetrahydronaphthalene as colorless crystals, m.p. 113-114.5 ° C. The yield is 46.5% (calculated on 2-bromo-1-oxo-1,2,3,4-tetrahydronaphthalene).

Melting point: 113 to 114.5 ° C (from methylene chloride, diethyl ether and n-hexane).

IR (KBr): 1 361, 1 340, 1 206, 1 175, 1 141, 1 033, 1 060, 1 050, 981, 959, 949, 917, 847, 781, 768, 625, 546, 530, 510 cm ¹ .

NMR (CDCl ₃ ): δ 2.37 (2H, m), 2.9 (2H, m), 2.94 (3H, s), 2.98 (3H, s), 3.43 (3H, s) )

5.27 (1H, t, J = 3Hz), 7.17 (3H, m), 7.63 (1H, m).

H, 6.34; S, 11.20. Found: C, 54.73; H, 6.36.

Example 45

In a similar manner to Example 32, 2-bromo-1- (4-difluoromethoxyphenyl) -1-oxopropane was prepared as a colorless oil from 1- (4-difluoromethoxyphenyl) -1-oxopropane.

NMR (CDCl 3): δ 1.92 (3H, d, J = 7Hz), 5.23 (1H, q, J = 7Hz), 6.58 (1H, t, J = 72Hz), 15 (2H, d, J = 9Hz), 8.00 (2H, d, J = 9Hz).

Example 46

In a similar manner to Example 17, 1- (4-difluoromethoxyphenyl) -2-hydroxy-1-oxopropane dimethylacetal was prepared as a colorless oil from 2-bromo-1- (4-difluoromethoxyphenyl) -1-oxopropane.

IC (neat): 3,600-3,200, 1,515, 1,385, 1,230, 1,130, 1,050, 840 cm ^-1 .

NMR (CDCl ₃ ): δ 0.95 (3H, d, J = 7Hz), 2.37 (1H, d, J = 3Hz), 3.23 (3H, s), 3.33 (3H, s), 4.10 (1H, dq, J = 3 and 7Hz), 6.52 (1H, t, J = 74Hz), 7.10 (2H, d,

J = 9 Hz), 7.49 (2H, d, J = 9 Hz).

Example 47

In a similar manner to Example 7, 1- (4-difluoromethoxyphenyl) -2-hydroxy-1-oxopropane dimethyl acetal obtained in Example 46 was prepared as 1- (4-difluoromethoxyphenyl) -2-methanesulfonyloxy-1-oxopropane dimethylacetal as a colorless oil. The yield is 55% (calculated on 1- (4-difluoromethoxyphenyl) -1-oxopropane).

IC (neat): 1,515, 1,360, 1,235, 1,180, 1,130, 1,100, 1,070, 1,045, 975, 920, 540, 530 cm ^-1 .

NMR (CDCl ₃ ): δ 1.18 (3H, d, J = 7 Hz), 3.09 (3H, s), 3.15 (3H, s), 3.18 (3H, s), 4, 98 (1H, q, J = 7Hz), 6.53 (1H, t, J = 74Hz), 7.10 (2H, d, J = 9Hz), 7.45 (2H, d, J = 9 Hz).

Example 48

In a similar manner to Example 32, 2-bromo-1- (4-difluoromethoxyphenyl) -3-methyl-1-oxobutane was prepared as a colorless oil from 1- (4-difluoromethoxyphenyl) -3-methyl-1-oxobutane.

IC (neat): 1690, 1660, 1230, 1120, 1055 cm ^-1 .

NMR (CDCl 3): δ 1.02 (3H, d, J = 7 Hz), 1.21 (3H, d, J = 7 Hz), 2.1 to 2.8 (1H, m), 4.85 (1H, d, J = 9Hz), 6.60 (1H, t, J = 74Hz), 7.18 (2H, d, J = 9Hz) 8.03 (2H, d, J = 9Hz) ).

Example 49

In a similar manner to Example 17, 1- (4-difluoromethoxyphenyl) -2-hydroxy-3-methyl-1-oxobutane dimethylacetal was prepared from 2-bromo-1- (4-difluoromethoxyphenyl) -3-methyl-1-oxobutane in the form of colorless oil.

IC (neat): 3,600-3,300, 1,515, 1,390, 1,230, 1,130, 1,050 cm ^-1 .

NMR (CDCl ₃ ): δ 0.69 (3H, d, J = 6Hz), 0.88 (3H, d, J = 6Hz), 1.2-1.7 (1H, m),

2.50 (1H, d, J = 3Hz) 3.22 (3H, s), 3.24 (3H, s), 3.70 (1H, dq, J = 3 and 6Hz),

6.50 (1H, t, J = 74Hz), 7.07 (2H, d, J = 9Hz), 7.52 (2H, d, J = 9Hz).

Example 50

In a similar manner to Example 13, 1- (4-difluoromethoxyphenyl) -2-hydroxy-3-methyl-1-oxobutane dimethylacetal gave 1- (4-difluoromethoxyphenyl) -2-methanesulfonyloxy-3-methyl-1-oxobutane dimethylacetal as colorless oil. The yield is 76% (calculated on 1- (4-difluoromethoxyphenyl) -3-methyl-1-oxobutane). On standing at low temperatures, this product crystallizes. Melting point: 60-61 ° C.

IR (KBr): 1,515, 1,350, 1,230, 1,180, 1,145, 1,080, 1,055, 1,035, 975 cm ^-1 .

NMR (CDCl 3): δ 0.67 (3H, d, J = 6Hz), 0.91 (3H, d, J = 6Hz), 1.4-1.9 (1H, m), 3.17 (3H, s), 3.19 (3H, s), 3.22 (3H, s), 4.75 (1H, d, J = 4Hz), 6.50 (1H, t, J = 74) Hz), 7.08 (2H, d, J = 9Hz), 7.50 (2H, d, J = 9Hz).

Example 51

230 mg of sodium metal are dissolved in 3 ml of anhydrous methanol and 2 ml of the solution are added

1.43 g of 2-bromo-1- (4-ethoxyphenyl) -3-methyl-1-oxobutane in anhydrous methanol. The mixture was stirred at room temperature for 1.5 hours and then at 50 ° C for 45 minutes. Conventional work-up gave 1.444 g of crude product, i.e. 1- (4-ethoxyphenyl) -2-hydroxy-3-methyl-1-oxobutane dimethylacetal, which, without further purification, formed a colorless oily substance. The crude product was subjected to the reaction described in Example 52.

IR (neat): 3,600-3,300, 1,610, 1,515, 1,485, 1,400, 1,250, 1,175, 1,115, 1,050, 990,

925,840,810 cm ^-1 .

NMR (CDCl 3): δ 0.68 (3H, t, J = 6Hz), 0.87 (3H, d, J = 6Hz), 1.39 (3H, t, J = 7Hz),

1.2-1.7 (1H, m), 2.50 (1H, d, J = 3Hz), 3.22 (3H, s), 3.24 (3H, s), 3.68 (1H , d, J = 3 and 5 Hz), 4.01 (2H, q, J = 7Hz), 6.82 (2H, d, J = 9Hz), 7.37 (2H, d, J = 9Hz) Hz).

Example 52

Following the procedure of Example 13, 1- (4-ethoxyphenyl) -2-hydroxy-3-methyl-1-oxobutane dimethyl acetal obtained in Example 51 was prepared using 1- (4-ethoxyphenyl) -2-methanesulfonyloxy-3-methyl- 1-oxobutane in the form of colorless crystals. The yield is 62% based on 2-bromo-1- (4-ethoxyphenyl) -3-methyl-1-oxobutane).

Melting point: 83-87 ° C.

IR (KBr): 1610, 1335, 1260, 1245, 1175, 955, 850, 840 cm ^-1 .

NMR (CDCl ₃ ): δ 0.71 (3H, d, J = 6Hz), 0.94 (3H, d, J = 6Hz), 1.40 (3H, t, J = 7Hz),

1.5-1.9 (1H, m), 3.18 (3H, s), 3.20 (3H, s), 3.24 (3H, s), 4.02 (2H, q, J = = 7 Hz), 4.57 (1H, d, J = 3Hz), 6.85 (2H, d, J = 9Hz), 7.37 (2H, d, J = 9Hz).

Example 53

In the same manner as in Example 51, 2.58 g of 1- (4-methoxyphenyl) -2- (2-bromo-phenyl) -2-dimethylacetal product were prepared from 2.71 g of 2-bromo-1- (4-methoxyphenyl) -3-methyl-1-oxobutane. hydroxy-3-methyl-1-oxobutane as a colorless oil and subjected to the reaction described in Example 54 without purification.

IR (neat): 3,600-3,300, 1,615, 1,515, 1,255, 1,175, 1,115, 1,045, 840 cm ^-1 .

NMR (CDC1 _3): delta 0.70 (3H, d, J = 6Hz), 0.87 (3H, d, J = 6Hz), '1.2 to 1.7 (1H, m), 2 53 (1H, broad s), 3.33 (3H, s), 3.34 (3H, s), 3.69 (1H, d, J = 5 Hz), 3.78 (3H, s) 6.83 (2H, d, J = 9Hz); 7.40 (2H, d, J = 9Hz).

Example 54

2.58 g of 1- (4-methoxyphenyl) -2-hydroxy-3-methyl-1-oxobutane dimethylacetal obtained in Example 53 are dissolved in 5 ml of anhydrous pyridine and the solution is stirred under ice-cooling.

2.00 g of methanesulfonic anhydride were added to the solution, and the mixture was stirred under ice-cooling for 4 hours and then at room temperature for 2 hours. To the mixture was added 20 ml of water and stirred at room temperature for 1 hour, and then extracted 3 times with 20 ml of diethyl ether. The extracts were washed twice with 5 ml of water, dried over anhydrous magnesium sulphate and evaporated under reduced pressure. The oily residue was purified by column chromatography (Florisil, methylene chloride) to give 3.10 g of Γ- (4-methoxyphenyl) -2-methanesulfonyloxy-3-methyl-1-oxobutane dimethyl acetal as a colorless oil. Upon standing at room temperature, this compound crystallized. The yield is 93% (calculated on 2-bromo-1- (4-methoxyphenyl) -3-methyl-1-oxobutane).

Melting point: 71.5-73 ° C.

IR (KBr): 1620, 1525, 1355, 1260, 1180, 1 105, 1055, 980, 970, 960, 945, 865, 850 cm ^-1 .

NMR (CDCl 3): δ 0.69 (3H, d, J = 6Hz), 0.89 (3H, d, J = 6Hz), 1.5-1.9 (1H, m), 3.14 (3H, s), 3.16 (3H, s), 3.21 (3H, s), 3.76 (3H, s), 4.72 (1H, d, J = 4 Hz),

6.82 (2H, d, J = 9Hz); 7.36 (2H, d, J = 9Hz).

Example 55

To a stirred suspension of 0.65 g of sodium hydride (55% in mineral oil) in 10 ml of anhydrous tetrahydrofuran was added 2.7 ml of ethylene glycol under ice-cooling. After stirring at room temperature for 40 minutes, 2.71 g of 2-bromo-1- (4-methoxyphenyl) -3-methyl-1-oxobutane was added to the reaction mixture, and the mixture was stirred at 60 ° C for 12 hours. Water (50 ml) was added to the reaction mixture, followed by extraction with methylene chloride (3 x 30 ml). The extracts were washed with 10 ml of water, dried over magnesium sulphate and evaporated under reduced pressure. The oily residue was subjected to column chromatography (Florisil, methylene chloride) to give 719 mg of 2-hydroxy-1- (4-methoxyphenyl) -3-methyl-1-oxobutane ethylene acetal as a colorless oil. Yield 29%.

IR (neat): 3,600-3,400, 1,620, 1,520, 1,255, 1,175, 1,040, 845 cm ^-1 .

NMR (CDCl ₃ ): δ 0.88 (3H, d, J = 6Hz), 0.90 (3H, d, J = 6Hz), 1.2-1.7 (1H, m),

2.55 (1H, broad d, J = 5 Hz), 3.5 to 4.2 (5H, m), 3.77 (3H, s), 6.83 (2H, d,

J = 9 Hz), 7.36 (2H, d, J = 9 Hz).

Example 56

In a similar manner to Example 13, 1- (4-methoxyphenyl) -2-methanesulfonyloxy-3-methyl-1-oxobutane ethylene acetal was prepared from 2-hydroxy-1- (4-methoxyphenyl) -3-methyl-1-oxobutane ethylene acetal in in the form of colorless crystals. Yield 78%.

Melting point: 82-83 ° C.

IR (KBr): 1610, 1510, 1335, 1250, 1170, 1050, 970, 940, 930, 815 cm ^-1 .

NMR (CDCl ₃ ): δ 0.91 (6H, d, J = 7 Hz), 1.5-1.9 (1H, m), 2.99 (3H, s), 3.6-4.2 (4H, m), 3.75 (3H, s), 4.67 (1H, d, J = 4Hz), 6.83 (2H, < 3, J = 9Hz), 7.34 (2H, d, J = 9Hz).

Example 57

In the same manner as in Example 35, 1- (6-methoxy-2-naphthyl) -2- dimethyl acetal was prepared from L-10-camphorsulfonyl chloride and 1- (6-methoxy-2-naphthyl) -2-hydroxy-1-oxopropane dimethylacetal. (L-10-camphorsulfonyloxy) -1-oxopropane as a mixture of the 2 diastereomers. The mixture was recrystallized twice from methanol to give one of the diastereomers (m.p. 93-96 ° C, λ = 32.2 ° (c = 0.801, chloroform)) as colorless plate-like crystals. This product fully agrees in the 1C and NMR spectral data with one of the 1- (6-methoxy-2-naphthyl) -2- (D-10-camphorsulfonyloxy) -1-oxopropane dimethylacetal dimethylacetal prepared in Example 35.

The starting L-10-kamforsulfonylch.lorid was prepared from commercial L-10-camphorsulphonate ammonium j (o?) ^ ² = -18.4 ° (c = 5.3, vodajj and thionyl chloride as described by H. Sutherland RL Shriner, J. Am. Chem. Soc., 58, 62 (1936). [.Alpha.] D @ 20 = -32.3 DEG (c = 1.36 DEG chloroform), m.p. 58-64 DEG.

Example 58

799 mg of 1- (6-methoxy-2-naphthyl) -2-hydroxy-1-oxopropane dimethylacetal are dissolved in 3 ml of anhydrous pyridine and the solution is stirred at room temperature. To the solution was added 833 mg of p-toluenesulfonyl chloride and the mixture was stirred at room temperature for 3 days. Water (30 ml) was added and the mixture was extracted successively with methylene chloride (3 x 10 ml). The extracts were dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The oily residue was purified by column chromatography (silica gel, methylene chloride) to give 1.019 g of 1- (6-methoxy-2-naphthyl) -2-p-toluenesulfonyloxy-1-oxopropane dimethylacetal as a colorless oil. Yield 81.9%.

IC (neat): 1612, 1489, 1360, 1278, 1192, 1178, 899, 560 cm ^-1 .

NMR (CDCl ₃ ): δ 1.13 (3H, d, J = 7 Hz), 2.40 (3H, s), 3.13 (3H, s), 3.21 (3H, s) 3.88 (3H, s), 5.04 (1H, q, J = 7Hz), 7.0-7.9 (10H, ra).

Example 59

To a solution of 132 mg of sodium metal in 5 ml of anhydrous methanol was added 879 mg of 1- (6-methoxy-2-naphthyl) -2-bromo-1-oxopropane. The mixture was stirred at room temperature for 7 hours. Water (20 ml) was added and the mixture was extracted successively with methylene chloride (3 x 10 ml). 2 drops of pyridine were added to the extracts, dried over anhydrous magnesium sulfate and then evaporated under reduced pressure to give crude 1- (6-methoxy-2-naphthyl) -2-hydroxy-1-oxopropane dimethylacetal. The crude product was dissolved in 2 ml of anhydrous pyridine without purification and the solution was stirred at room temperature. 0.60 ml of benzenesulfonyl chloride was then added to the solution and the mixture was stirred for 20 hours. Water (10 ml) was added and the mixture was extracted successively with methylene chloride (3 x 10 ml). The extracts were washed with 10 ml of water, dried over anhydrous magnesium sulphate and evaporated under reduced pressure. The oily residue was purified by column chromatography (silica gel, methylene chloride) to give 1.024 g of 1- (6-methoxy-2-naphthyl) -2-benzenesulfonyloxy-1-oxopropane dimethylacetal as a colorless oil. The product yield is 82.0% (based on 1- (6-methoxy-2-naphthyl) -2-bromo-1-oxopropane).

IR (neat): 1637, 1612, 1488, 1456, 1365, 1278, 1190, 925, 900, 761, 598 cm ^-1

NMR (CDCl ₃ ): δ 1.15 (3H, d, J = 7Hz), 3.10 (3H, s), 3.18 (3H, s), 5.08 (1H, q, J = = 7 Hz), 7.0 to 8.1 (11H, m).

SUBJECT OF THE INVENTION

Claims (6)

SUBJECT OF THE INVENTION A process for the preparation of acetals of alpha-sulfonyloxy ketones of the general formula II OR ² OSCK-R ⁵ Λ I, “1 in which Ar stands for a) phenyl which is optionally substituted by halogen, C ^^ - alkyl, <?! _ g -alkoxy, C ₁ _G alkanoylamino, C ₁ _G-haloalkyl, phenyl or oxo-2-isoindolinyl group, naphthyl, which is optionally substituted with C 1-8 -alkoxy or c) a thienyl group, R ¹ represents a hydrogen atom or a C 1-6 -alkyl group, or Ar and R ¹ optionally form a fused ring with the carbon atom to which they are attached; R ³ and R ⁴ independently represent C 1-6 alkyl; or together represent a C 2-6 alkylene group, R is a C 1-8 -alkyl group, a phenyl group optionally substituted by a halogen atom or a C 1-8 -alkyl group, or a camphoryl group, and optionally diastereomers thereof, characterized in that they are reacted a compound of formula V 0 X Ar - Ih (V), in which X represents a halogen atom of the formula and Ar and R with an alkali metal alkoxide, R ³ , where M is an alkali metal and R is as defined above, wherein for the preparation of compounds of the formula II wherein R and R have the same meaning and Ar, R * and R $ are as defined above, the reaction of the above compound of formula V is carried out in the presence of an alcohol of the formula R ³ OH wherein R ^J is as defined above, to give a compound of formula VI GR ⁴ (VI), Where R and R have the same meaning and denote a C 1-6 -alkyl group, Ar and R are as defined above, and for the preparation of compounds of formula II wherein R ³ and R ⁴ are different and are The C 1-4 alkyl group, Ar, R and R are as defined above, the epoxy compound of formula VII formed after reaction of the above compound of formula V with said alkali metal alkoxide Ar OR ³ AND C-CH (VII), wherein Ar, are as defined above, is reacted with an alcohol of formula R OH, wherein R ⁴ is as defined above, in the presence of an alkali metal alkoxide of the general formula R ⁴ OM, wherein R ⁴ is as defined above and M is an alkali metal, to form a compound of general formula VI where R and R are different and represent C _first-alkyl, Ar and R are as ^1-4 3 4 as above, and optionally for the preparation of compounds of formula II wherein R and R 1 together represent C ₂ 5 _G-alkylene, Ar, R and R are as defined above, reacting a compound of the above formula V with an alkylene glycol of the formula HO-R-OH, where R is a C _1-6 -alkylene group, to form a compound of formula VI wherein R aa 1 R together denote _a C .- ^ alkylene, Ar and R are as defined above, and the resultant * | 3 4 compounds of the formula VI wherein Ar and R are as defined above, R and R each independently represent C ₁ _ ₄ ~ alkyl group or together represent a C ₂ _ _6-alkylene group, is reacted with a compound of formula R ⁵ - SO 2 - Hal or (R ⁵ - SO ₂ ) ₂ O, wherein R is as defined above and Hal represents a halogen atom. 2. A process according to claim 1, wherein the compounds of the formulas V, VII and VI above are used in which. Ar is 6-methoxy-2-naphthyl, 4-isobutylphenyl group, 4-C ₃ _G-alkoxyphenyl, 4-fluormethoxyfenylovou group, 2-thienyl, 4- (l-oxo-2-isoindolinyl) -phenyl, 4-biphenylyl and 4- (tert-butyl) phenyl. 3. A process according to claim 1, wherein the compound of formula VI is 1- (6-methoxy-2-naphthyl) -2-hydroxy-1-oxopropane dimethylacetal. 4. A process according to claim 1, wherein the compounds of formula (VI) having the corresponding meanings given above for each substituent are used to form 1- (6-methoxy-2-naphthyl) -2-methanesulfonyloxy-1-oxo, propane dimethylacetal. . 5. A process according to claim 1, wherein the compounds of formula (VI) having the corresponding meanings given above for each substituent are used to give 1- (6-methoxy-2-naphthyl) -2- (D-10-camphorsulfonyloxy) dimethyl acetal. -1-oxopropane. 6. A process according to claim 1, wherein the compounds of formula (I) are used VI with the corresponding meanings given above for the individual substituents to give 1- (6-methoxy-2-naphthyl) -2- (D-10-camphorsulfonyloxy) -1-oxopropane dimethyl acetal diastereomer.