Preparation method of (S)-4-hydroxy-2-oxo-1-pyrrolidineacetamide

Abstract

The invention discloses a preparation method of (S)-4-hydroxy-2-oxo-1-pyrrolidineacetamide. The method comprises the following steps: reacting glycine ethyl ester hydrochloride and (S)-4-halo-3-hydroxy-ethyl butyrate serving as raw materials in the presence of an alcohol solvent under an alkaline condition; filtering, washing, concentrating, extracting, separating, introducing ammonia water to obtain a crude product, and purifying the crude product, wherein the glycine ethyl ester hydrochloride is dissociated into glycine ethyl ester by using diethyl ether and ammonia gas, the alcohol solvent is absolute methanol or absolute ethyl alcohol, and the alkali is sodium carbonate or sodium bicarbonate. The (S)-4-halo-3-hydroxy-ethyl butyrate and the glycine ethyl ester hydrochloride are taken as major raw materials, so that the raw materials are cheap, readily available and environmentally friendly; the glycine ethyl ester hydrochloride is dissociated, so that the using quantities of the materials in reaction are reduced, the cost is reduced, and meanwhile the reaction yield is increased. The preparation method is low in preparation cost, the yield can be up to 36 percent, the reaction conditions are mild, the industrial mass production is facilitated, and the HPLC (High Performance Liquid Chromatography) purity of an obtained (S)-oxiracetam product is over 98.5 percent.

Description

[0001] The application of the present invention is a divisional application with application number 201110024500.5, application date January 21, 2011, and invention title "Method for preparing (S)-4-hydroxy-2-oxo-1-pyrrolidineacetamide". technical field [0002] The present invention relates to the preparation of (S)-4-hydroxyl-2-oxopyrrolidine derivatives, in particular to the preparation method of (S)-4-hydroxyl-2-oxo-1-pyrrolidineacetamide, which belongs to chemical synthesis field. Background technique [0003] Oxiracetam is a nootropic drug synthesized for the first time in 1974 by the Italian Skelebechem Company. The drug was launched in Italy in 1987. Oxiracetam is composed of two isomers (S) - A racemate of oxiracetam ((S)-oxiracetam) and (R)-oxiracetam ((R)-oxiracetam). The report on oxiracetam discloses that it is a synthetic hydroxyaminobutyric acid (GABOB) cyclic derivative, which can promote ATP in the brain, promote the synthesis of acetylcholine and enhance t...

AI Technical Summary

Problems solved by technology

[0004] Regarding the report on the synthesis of (S)-oxiracetam, US Patent No. 4,797,496 and WO93 / 06826 disclose the method for preparing (S)-oxiracetam. The method disclosed in this document includes obtaining chiral 3,4-epoxybutyrate, react the resulting product with N-protected glycinamide, and make the resulting product carry out N deprotection, then obtain optically pure oxiracetam through cyclization, the steps of this method are relatively few, but due to The synthesis yield of chiral 3,4-epoxybutyrate is extremely low and the cost of this method is high

U.S. Patent US4173569 describes another (s)-oxiracetam synthesis method: using (s)-γ-amino-β-hydroxybutyric acid as the starting material, protecting the hydroxyl group with a silylating agent, and after cyclization The product of the product is reacted with ethyl haloacetate, and the reaction product is deprotected, ammonolysis, and finally obtains the target compound; this preparation method is not suitable for industrial scale production, and the use of protecting groups to protect the hydroxyl group will increase the reaction steps and waste raw materials , takes a long time, increases the cost, and reduces the total yield

Images