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

Abstract

The invention relates to a preparation method of (S)-4-hydroxy-2-oxo-1-pyrrolidineacetamide. The preparation method comprises the following steps of: taking glycine ethyl ester hydrochloride and ethyl-(S)-4-halo-3-hydroxy-butanoate as raw materials, reacting in an alcohol solvent under alkaline conditions, washing with an inorganic alcohol, concentrating, extracting, separating, and introducing ammonia water to get a crude product of the (S)-4-hydroxy-2-oxo-1-pyrrolidineacetamide; and performing purification treatment on the crude product, wherein the glycine ethyl ester hydrochloride firstly needs to adopt ethyl ether and ammonia gas to dissociate so as to get glycine ethyl ester. The main raw materials adopted in the preparation method disclosed by the invention are the ethyl-(S)-4-halo-3-hydroxy-butanoate and the glycine ethyl ester hydrochloride, and the raw materials are low in price, easy to obtain, environment-friendly and pollution-free; and according to the preparation method disclosed by the invention, dissociation treatment is firstly performed on the glycine ethyl ester hydrochloride, thus the using quantity of the materials in the reaction is effectively reduced, the cost is lowered, and a positive role is simultaneously played for the reaction yield. (S)-oxiracetam prepared by the preparation method disclosed by the invention has low cost, high yield which is as high as 36% and mild reaction conditions, and is conductive to industrialized large-scale production, and the HPLC (high-performance liquid chromatography) purity of the prepared (S)-oxiracetam product is above 98.5%.

Description

technical field [0001] 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 [0002] 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 the conduction of nerve excitation, and it can prevent retrograde neuropathy caused by hypoxia. Sexual amnesia has improvement effect, can enhance memory, improve learning ability, is one of effective drugs for treating diseases such as Alz...

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Problems solved by technology

[0003] 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

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