Method for preparing (S)-4-hydroxy-2-oxo-1-pyrrolidine acetamide

Abstract

The invention discloses a method for preparing (S)-4-hydroxy-2-oxo-1-pyrrolidine acetamide. The method comprises the following steps: reacting glycine ethyl ester hydrochloride and (S)-4-halo-3-hydroxy-ethyl butyrate as raw materials in an alcohol solvent under an alkaline condition, washing by inorganic alcohol, concentrating, subsequently separating, feeding ammonia water so as to obtain a crude product, and performing purification treatment on the crude product, wherein the glycine ethyl ester hydrochloride needs to be freed into glycine ethyl ester by diethyl ether and ammonia gas. The (S)-4-halo-3-hydroxy-ethyl butyrate and glycine ethyl ester hydrochloride are used as the main raw materials which are low in price, easily available, environmentally friendly and free of pollution; as the glycine ethyl ester hydrochloride is firstly subjected to free treatment, the use amount of the raw materials in the reaction is effectively reduced, the cost is lowered, and meanwhile, the yield of the reaction is beneficially improved. With the method, the cost for preparing (S)-oxiracetam is low, and the yield can be as high as 36%; the reaction condition is mild, and thus the method is beneficial to industrial scale production; the HPLC (High Performance Liquid Chromatography) purity of the prepared (S)-oxiracetam product is greater than 98.5%.

Description

[0001] The application of the present invention is a divisional application with application number 201110024496.2, application date of January 21, 2011, and the title of the invention "(S)-4-hydroxy-2-oxo-1-pyrrolidineacetamide preparation method". technical field [0002] The invention relates to the preparation of (S)-4-hydroxy-2-oxopyrrolidine derivatives, in particular to a preparation method of (S)-4-hydroxy-2-oxo-1-pyrrolidine acetamide, which belongs to chemical synthesis field. Background technique [0003] Oxiracetam (oxiracetam) is a nootropic drug first synthesized by the Italian company Scribble in 1974. The drug was launched in Italy in 1987. Oxiracetam is composed of two isomers (S) - a racemate composed of oxiracetam ((S)-oxiracetam) and (R)-oxiracetam ((R)-oxiracetam). The report on oxiracetam discloses that it is a synthetic cyclic derivative of hydroxyaminobutyric acid (GABOB), which can promote ATP in the brain, promote the synthesis of acetylcholine and...

AI Technical Summary

Problems solved by technology

[0004] Regarding the report on the synthesis of (S)-oxiracetam, U.S. Patent 4,797,496 and WO 93 / 06826 disclose the method for preparing (S)-oxiracetam. The method disclosed in this document includes obtaining chiral β-hydroxybutyrolactone from chiral 3,4-epoxybutyrate, reacting the resulting product with N-protected glycinamide, and carrying out N-deprotection of the resulting product, followed by cyclization to obtain optically pure oxiracetam, the method has relatively few steps, but The process is costly due to the very low yield of chiral 3,4-epoxybutyrate synthesis

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