JPS5857341A - Preparation of dialkyl 2-oxo-3-benzylsuccinate - Google Patents

Abstract

PURPOSE:To obtain the titled substance useful as various synthetic intermediates easily from inexpensive raw materials, by reacting an alkali metallic salt of a dialkyl oxalacetate with a halogenated benzyl halide or benzyl sulfonate in an organic solvent. CONSTITUTION:A compound of formulaI(R is lower alkyl; M is alkali metal) is reacted with a compound of formula II (X is halogen atom or group R'SO3-; R' is alkyl or aryl) in an organic solvent, e.g. alcohol, hydrocarbon or dimethylformamide (DMF), at 60-120 deg.C for 1-24hr to give a compound of formula III. EFFECT:The aimed substance can be prepared from the inexpensive and easily handleable raw materials industrially and advantageously.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel method for producing 2-oxo-3-benzylsuccinic acid difurkyl ester represented by the general formula (wherein R represents a lower alkyl group).

2-Oxo-3-benzylsuccinic acid dialkyl ester is converted into benzyl malonic acid sialic ester by heating and decarbonylation, and is converted into 2-oxo-4- by hydrolysis with acid. It is a chemical compound that is of great concern as an intermediate for the synthesis of various useful compounds, such as by converting it into phenylbutyric acid. Conventionally, ethyl 3-phenylpropionate and diethyl oxalate are mixed with sodium or sodium ethoxychloride in ether. A method of condensation in the presence of a base such as Bar, etc. is known.
31 555 (1898)).

Shikashi, in this known method, the main raw material, ethyl 3-phenylpropionate, is expensive, and the sodium and sodium ethoxide used as the base are highly reactive, so be very careful when handling large quantities! Things to do,
This cannot be said to be an industrially suitable method.

The purpose of the present invention is to provide an industrially advantageous method for producing 2-oxo-3-benzylsuccinic acid cyflu'tk ester from inexpensive and easy-to-handle raw materials,
According to the present invention, an alkali metal salt of oxalacetic acid difurkyl ester represented by the general formula (1) (wherein R is a lower alkyl group and M is an alkali metal) and a general 2〇) c/-Cli ( ...) (wherein, X is a halogen atom or an R1508 group, and R' is an alkyl group or a 7-aryl group) is reacted with a halogenated benzyl or sulfonic acid henzyl ester in an organic solvent to obtain the desired product. easily (
Manufacture can be obtained.

This invention (in the formula 0, the substituent R is a carbon number 1 such as methyl, ethyl, propyl, butyl, hexyl, etc.)
-6 lower furkyl groups are mentioned, and M is an alkali metal such as sodium or potassium. In particular, diethyl acetate sodium salt in which R is an ethyl group and R is sodium is a compound that can be produced at low cost from diethyl oxalate and ethyl acetate.

In addition, examples of the benzyl halide or benzyl sulfonate indicated in 2〇), which is one of the raw materials, include benzyl chloride, benzyl bromide, benzyl methanesulfonate,
Benzyl para-toluenesulfonate and the like are preferably used.

This reaction is usually carried out in an organic solvent, and alcohols such as methanol, ethanol, propatool, butanol, and hexanol, aromatic hydrocarbons such as benzene and toluene, and aliphatic carbons such as hexane and octane are used. Examples include hydrogen, ethers such as diethyl ether and tetrahydrofuran, ketones such as acetone and methyl ethyl ketone, esters such as ethyl acetate, dimethylformazide, and dimethyl sulfoxide. An alkali metal salt of oxalacetic acid sial Φylester is dissolved or suspended in an organic solvent, and a benzyl halide or a benzyl sulfonate ester is added thereto to carry out the reaction. Equivalent amounts of each raw material are sufficient, but one or the other may be used in slightly excess. The reaction temperature is -10 to 150C, preferably 600C to 150C.
It is 20C. Moreover, the reaction time is -1 to 24 hours. The progress of the reaction can be monitored by thin-layer coomadography, and the completion of the reaction can be confirmed when the reaction solution becomes neutral. After the reaction is complete, if insoluble matter is present, filter it out, distill off the solvent, and mix it with water and a water-immiscible solvent (
For example, ether, toluene, etc.) are used to extract the product, followed by an aqueous alkaline solution.

After making the alkaline aqueous solution acidic with an acid such as hydrochloric acid or sulfuric acid,
After extraction with an organic solvent again, the organic layer is concentrated to obtain the desired dialkyl 2-oxo-3-benzylsuccinate.

Hereinafter, this will be explained in detail using examples.

Example 1 Add 110 d of ethyl alcohol to 30 f of sodium diethyl acetate and heat in a bath [E100CC].

While heating, 25 f of benzyl chloride is added dropwise over 1 hour.

After dropping, the mixture was further heated at the same temperature for 6 hours. After the reaction is completed, the precipitated II)ium bromide is filtered off. After distilling off ethanol from the filtrate under reduced pressure, water 100w/, toluene 1
Add 001Ij and extract. An extraction operation is performed by adding 100% of an aqueous solution of sodium hydroxide to the toluene layer.

Add concentrated hydrochloric acid little by little to the alkaline water layer while cooling.
Make acidic. After extraction with 100 liters of toluene and drying the toluene layer with anhydrous sulfuric acid (IJ), the toluene was distilled off to give diethyl 2-oxo-3-benzyl succinate as a yellow oil. Of (yield g 3 %) was obtained. In addition, the nuclear magnetic resonance spectrum of ice crystals (CDCl, )
are 1.08 (3H,t), 1.21 (3H
.

t) 13.20 (2B (keto type), d)
, 3.77 (2H(z/−/L, type), S),
4.03 (2H+Q)+4.17 (2H+q), 4
．． 35 (IH (keto type), 1).

7.18 (5H,S), 12.75 (IH (enol type).

A signal was observed in S), which was consistent with that produced by a known method in Reference Example below.

Example 2 Dimethylformamide 1001E/C, 25F diethyl acetate sodium salt and 15F benzyl chloride are added and heated at a pass temperature of Zoo for 6 hours. After the reaction was completed, dimethylformacide was distilled off under reduced pressure, and 100 d of water was added.
, diethyl ether 100++j is added and extracted. After extraction is performed by adding 10% of aqueous potassium hydroxide solution to the ether layer, 1% concentrated hydrochloric acid is added little by little to the alkaline aqueous layer under cooling to make it acidic. After extraction with 100 d of ether and drying the ether layer over anhydrous sodium sulfate, the ether was distilled off to obtain 18.3 t of diethyl 2-oxo-3-benzylsuccinate (yield ss, 6%).

Example 3 100 ml of acetone, 25 f of dimethyl potassium salt of acetic acid, and 36 f of benzyl para-toluenesulfonate are added and heated at a bath temperature of 90 [for -5 hours. After filtering off insoluble matter, acetone was distilled off under reduced pressure, and the same treatment as in Example 1 was performed to obtain 18.3f (yield: 53.2%) of dimethyl 2-oxo-3-benzylsuccinate. .

Reference Example 5.3f of sodium ethoxide is added to 50IIIj of diethyl ether and cooled to 20C. Diethyl oxalate 10.9 F and ethyl 3-phenylpropionate 11.
5. Add the mixture with F to the above ether solution at a temperature of 15 to 2.
Add dropwise over 20 minutes while maintaining 0 Cr.

After completion of the dropwise addition, stirring was continued for 24 hours at room temperature. After the reaction is completed, 2N hydrochloric acid 50-j is added and extracted. 5 in the ether layer
After extraction by adding aqueous sodium hydroxide solution,
After making the alkaline layer acidic by adding concentrated hydrochloric acid little by little, it was extracted with ether 5011F7. After drying the ether layer over anhydrous sodium sulfate, the ether was distilled off to obtain 1 t, ot of diethyl 2-oxo-3-benzylsuccinate (yield: 61 oz).

Patent applicant: Ajinomoto Co., Inc.

Claims (1)

[Claims] An alkali metal salt of oxalacetic acid dialkyl ester represented by the general formula ([) (wherein 8 represents a lower alkyl group and y represents an alkali metal) and the general formula value) where X is a hapgen atom or R'80.- group, R1
is an alkyl group or an aryl group) with a benzyl hagenide or a pendyl ester sulfonate represented by the general formula (2) (wherein, Company R has the same meaning as above). ) A method for producing a 2-oxo-3-benzylsuccinic acid dialkyl ester represented by: