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

Abstract

The invention relates to a method for preparing (S)-4-hydroxide radical-2-oxo-1-pyrrolidine acetamide, which comprises the following steps: using (S)-4-halogen-3-poly 3-hydroxybutyrate and glycine amide or glycine amide hydrochloride as raw materials for reaction in alcoholic solvents under the alkaline condition to obtain crude products of the (S)-4-hydroxide radical-2-oxo-1-pyrrolidine acetamide, and carrying out pure treatment on the crude products. The method provided by the invention is characterized in that in the reaction under the alkaline condition, the pH value is controlled to be lower than or equal to 8.5 in the reaction through adding inorganic base for many times in the reaction process; the reaction is carried out under the conditions from the temperature rising to the backflow; and the purification treatment is realized by adopting ion exchange resin and recrystallization. The method disclosed by the invention uses the (S)-4-halogen-3-poly 3-hydroxybutyrate and glycineamide hydrochloride as main raw materials which are all commercially available goods, the raw materials have a low price, can be easily obtained and have environment-friendly and pollution-free effects. In the method disclosed by the invention, the preparation reaction period is short, the operation is simple and convenient, and the high performance liquid chromatography (HPLC) purity of prepared(S)-oxiracetam products is as high as more than 98.5 percent.

Description

technical field [0001] The present invention relates to a preparation method of (S)-4-hydroxy-2-oxo-1-pyrrolidineacetamide (commercial name is (S)-oxiracetam, the same below). Background technique [0002] Oxiracetam is a nootropic drug synthesized for the first time in 1974 by the Italian Shi Kebichem Company. It is composed of two isomers (S)-oxiracetam ((S)-oxiracetam) and (R)- Racemate of oxiracetam ((R)-oxiracetam). (S)-Oxiracetam is a single enantiomer of Oxiracetam, the chemical name is: (S)-4-hydroxy-2-oxo-1-pyrrolidineacetamide, and its chemical structure is as follows: [0003] [0004] According to WO93 / 06826, the two isomers of oxiracetam have different activities when used as brain function improvers, and the activity of (S)-oxiracetam is stronger than that of (R)-oxiracetam. [0005] The preparation method of (S)-oxiracetam in the patent WO2005 / 115978, wherein (S)-4-chloro-3-hydroxybutyrate and glycinamide react under alkaline conditions to obtain the fina...

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Problems solved by technology

[0005] The preparation method of (S)-oxiracetam in the patent WO2005 / 115978, wherein (S)-4-chloro-3-hydroxybutyrate and glycinamide react under alkaline conditions to obtain the final product oxiracetam The alkalinity of the reaction solution is controlled by one-time addition of alkali, but because oxiracetam is easily destroyed in a strong alkaline solution, this directly affects the yield of oxiracetam

[0006] In addition, in the preparation method of (S)-oxiracetam in the patent WO2005 / 115978, the reaction can be carried out at a temperature of 0-100°C, but in such a wide temperature range, the reaction efficiency varies greatly. Large, it still can not give a reaction temperature range with the highest product yield

[0007] In addition, silica gel column chromatography is used in the purification of the final product oxiracetam, and the eluent used is an organic mixed solvent. The amount of solvent is large, the pollution is large and difficult to recycle, the cost is high, and the silica gel column chromatography is not suitable Industrial production

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