JPH1171325A - Production of 4-aryl butanoic alkyl ester - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject compound useful as an intermediate for medicines, agrochemicals or the like by reacting a specific ester, as an easily obtainable stock compound, with a base. SOLUTION: This compound shown by formula II is obtained by reacting 3-oxo-2-(2-arylethyl)butanoic alkyl ester shown by formula I [Ar is a halogen, nitro or (substituted) phenyl; and R is a lower alkyl], obtained by reacting a p-arylethyl halide with an acetoacetic alkyl ester, with a base (e.g. sodium ethylate) in a reaction solvent (preferably methanol or the like) preferably at 20 to 100 deg.C, and post-treating the above product with an acidic, aqueous solution or water. The compound shown by formula II can be easily isolated and purified by treating the above reaction effluent by an adequate process, e.g. extraction, distillation or chromatography. The preferable molar ratio of the base is 0.1 to 5 and weight ratio of the reaction solvent is 2 to 5, both relative to the compound shown by formula I.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to 3-oxo-2-
The present invention relates to a method for producing alkyl 4-arylbutanoates using alkyl (2-arylethyl) butanoates as raw materials. Alkyl 4-arylbutanoates are useful as intermediates for pharmaceuticals, agricultural chemicals and the like. For example, it is used as an intermediate such as a medicine described in Japanese Patent Publication No. 8-510237.

[0002]

2. Description of the Related Art As a method for producing alkyl 4-arylbutanoates, a method of esterifying 4-arylbutanoic acids from acids and alcohols is known. Here, 4-phenylbutanoic acid as a raw material is produced from γ-butyrolactone and benzene using aluminum chloride (J. Am. Chem. Soc. 74 , 47).
21, (1952)), a method of producing from 3-benzoylpropionic acid using zinc is known (Or).
g. Synth. II, 499, (1943)). However, since these methods use a stoichiometric amount of aluminum chloride or zinc, there is a problem that a large amount of inorganic salts must be disposed of in a post-treatment, and the above-mentioned method using 4-arylbutanoic acids as a raw material is required. The production method is not necessarily an industrially advantageous method.

[0003]

SUMMARY OF THE INVENTION In view of the above, the present inventors have developed an industrially advantageous method for producing alkyl 4-arylbutanoates which does not require treatment of inorganic salts such as aluminum chloride and zinc. As a result of the investigation, it was found that 3-oxo- obtained easily by reacting β-arylethyl halide with alkyl acetoacetates.
The present inventors have found that the intended product can be easily produced by treating an alkyl 2- (2-arylethyl) butanoate with a base, and have reached the present invention.

[0004]

That is, the present invention provides a compound represented by the general formula [1]: (Wherein, Ar represents a phenyl group which may be substituted with a halogen atom, a nitro group or a lower alkyl group;
Represents a lower alkyl group. 3-oxo-2 represented by
A general formula [2] characterized by reacting an alkyl ester of-(2-arylethyl) butanoic acid with a base. (Wherein, Ar and R have the same meanings as described above).

[0005]

DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention will be described below in detail.
In the compounds represented by the general formulas [1] and [2],
A lower alkyl group is a straight or branched chain having 1 to 6 carbon atoms.
Is an alkyl group. As the halogen atom, fluorine,
Chlorine, bromine and iodine atoms. The alkyl 4-arylbutanoate of the present invention is 3-oxo-2-
It is obtained by reacting an alkyl (2-arylethyl) butanoate with a base and treating with an acidic aqueous solution or water.

The base used in the above reaction includes alkali metal alkoxides such as sodium ethylate, sodium methylate, sodium tert-butylate, potassium ethylate, potassium methylate, potassium tert-butylate, lithium carbonate and sodium carbonate. Carbonates of alkali metals and alkaline earth metals such as potassium carbonate, magnesium carbonate, calcium carbonate, strontium carbonate and barium carbonate; and alkali metal hydrogen carbonates such as lithium hydrogen carbonate, sodium hydrogen carbonate and potassium hydrogen carbonate. . The amount of the base used is 3-oxo-
It is usually 0.01 to 10 times, preferably 0.1 to 5 times the molar amount of the alkyl 2- (2-arylethyl) butanoate [1].

The reaction solvent is an alcoholic solvent such as methanol, ethanol, propanol, butanol, pentanol, hexanol and the like, an ether solvent such as ethyl ether, methyl-t-butyl ether, tetrahydrofuran and dioxane, pentane, hexane, toluene and benzene. Hydrocarbon solvents, monochlorobenzene, ethylene dichloride, halogenated hydrocarbon solvents such as chloroform, ethyl acetate and the like, preferably methanol, ethanol, propanol, butanol, pentanol,
It is an alcohol solvent such as hexanol. The amount of the reaction solvent to be used is usually 1 to 3 -oxo-2- (2-arylethyl) butanoic acid alkyl esters [1].
It is 10 to 10 times by weight, preferably 2 to 5 times by weight.

The reaction temperature depends on the kind of the base,
A range of 100 ° C. is preferred. After completion of the reaction, the target compound, an alkyl 4-arylbutanoate, can be obtained by post-treatment with an acidic aqueous solution or water. The alkyl 4-arylbutanoate [2] produced by such a reaction can be easily isolated and purified from the reaction mixture after the reaction by ordinary means, for example, extraction, distillation, or various chromatographic operations. Can be.

[0009]

According to the method of the present invention, an alkyl 4-arylbutanoate is obtained by using a readily obtainable alkyl 3-oxo-2- (2-arylethyl) butanoate [1] as a raw material. [2] can be produced by an industrially advantageous method

[0010]

EXAMPLES The present invention will be described in detail below with reference to examples, but the present invention is not limited to these examples. Example 1 In a nitrogen atmosphere, 0.471 g of ethyl 3-oxo-2- (2-phenylethyl) butanoate (2 mm
ol) and 1.295 g (4 mmol) of a 21% sodium ethylate / ethanol solution, refluxed for 8 hours, and then cooled to room temperature. Next, the mixture was quenched with a 1N aqueous hydrochloric acid solution, and extracted with toluene. Extraction solution was GC-I
As a result of analysis by the S method, ethyl 4-phenylbutanoate was obtained in a yield of 98%.

(Example 2) In Example 1, 1.295 g (4 mmo) of a 21% sodium ethylate / ethanol solution was used.
l) The procedure was performed in the same manner except that the amount was reduced to 0.194 g (0.6 mmol), and ethyl 4-phenylbutanoate was obtained in a yield of 90%.

Example 3 3-oxo- in a nitrogen atmosphere
Ethyl 2- (2-phenylethyl) butanoate 0.47
1 g (2 mmol), 1.41 g of ethanol and 0.553 g (4 mmol) of potassium carbonate were added, and the mixture was refluxed for 8 hours and then cooled to room temperature. Next, the mixture was quenched with a 1N aqueous hydrochloric acid solution, and extracted with toluene. Extraction solution is GC-
When analyzed by the IS method, ethyl 4-phenylbutanoate was obtained in a yield of 58%.

Claims (3)

[Claims] 1. The general formula [1] (Wherein, Ar represents a phenyl group which may be substituted with a halogen atom, a nitro group or a lower alkyl group;
Represents a lower alkyl group. 3-oxo-2 represented by
A general formula [2] characterized by reacting an alkyl ester of-(2-arylethyl) butanoic acid with a base. (Wherein, Ar and R have the same meanings as described above). 2. The process for producing alkyl 4-arylbutanoates according to claim 1, wherein the base is an alkali metal alkoxide, an alkali metal or alkaline earth metal carbonate or an alkali metal bicarbonate. 3. The amount of the base used is 3-oxo-2- (2-
3. The process for producing an alkyl 4-arylbutanoate according to claim 1 or 2, wherein the molar ratio is 0.1 to 5 times the molar amount of the alkyl (arylethyl) butanoate.