A preparation method of (s)-oxiracetam

Abstract

The invention relates to a preparation method of (S)-oxiracetam, which comprises the following steps: reacting raw materials glycine ethyl ester hydrochloride and ethyl (S)-4-halo-hydroxy-butyrate in an alcohol solvent under alkaline conditions, filtering, washing with inorganic alcohol, concentrating, extracting, concentrating the water phase, introducing stronger ammonia water to react to obtain a (S)-oxiracetam crude product, and carrying out purification treatment on the crude product. The glycine ethyl ester hydrochloride is firstly mixed with the alkali and alcohol solvent, and the raw material ethyl (S)-4-halo-hydroxy-butyrate is dropwisely added and the alkali is added in different batches to control the pH value of the reaction at 8-9. The purification treatment comprises the following steps: dissolving the (S)-oxiracetam crude product in a benign solvent to prepare a saturated solution at room temperature, and dispersing with a poor solvent in a closed environment. The HPLC (high performance liquid chromatography) purity of the prepared (S)-oxiracetam is up to 99.0% %, and the yield can be up to 33%; and the method is mild in reaction conditions, simple to operate and beneficial to industrial large-scale production.

Description

[0001] The application of the present invention is a divisional application with application number 201110023874.5, application date January 21, 2011, and invention title "Method for preparing (S)-oxiracetam". technical field [0002] The invention relates to a method for preparing oxiracetam, in particular to a method for preparing (S)-oxiracetam, which belongs to the field of chemical synthesis. 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 the conduction of nerve excitation, and it can prevent retrograde neuropathy caused by hypox...

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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 oxyracetam. The method disclosed in this document includes obtaining chiral alkyl3 , 4-epoxybutyrate, react the resulting product with N-protected glycinamide and make the resulting product carry out N deprotection, and then obtain optically pure oxyracetam through cyclization. The steps of this method are relatively few, but due to chiral The synthesis yield of alkyl 3,4-epoxybutyrate is extremely low and the cost of this method is high

U.S. Patent No. 4,173,569 has described another synthetic method of (s)-oxiracetam: (s)-lift-amino-thracene-hydroxybutyric acid is the starting material, the hydroxyl group is protected by a silylating agent, and the cyclization The final product is reacted with ethyl haloacetate, and the reaction product is through deprotection, ammonolysis, and finally obtains the target compound; this kind of 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 take a long time, increase the cost and reduce the total yield

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