2-oxo-1-pyrrolidine chiral derivative preparation method

Abstract

The present invention relates to a 2-oxo-1-pyrrolidine chiral derivative preparation method, which comprises: adding a chiral catalyst and a reaction solvent to a reaction container under the protection of an inert gas, and stirring for 15-40 min; adjusting the temperature to -80-30 DEG C, and adding a reaction raw material; adding a hydrogen source to the reaction container, and carrying out a constant temperature reaction for 8-48 h at a temperature of -80-30 DEG C; after completing the reaction, adjusting the temperature to -20-30 DEG C, adding a solution a and an substance b, and stirring for 8-12 h; carrying out an extraction treatment on the reaction material, and then carrying out drying, suction filtration and concentration on the organic layer to obtain a crude product; and carrying out re-crystallization on the crude product to obtain the product. The preparation method of the present invention has advantages of low production cost, high yield, easy industrial production, and the like.

Description

technical field [0001] The invention relates to the field of compound synthesis, in particular to a preparation method of 2-oxo-1-pyrrolidine chiral derivatives. Background technique [0002] 2-oxo-1-pyrrolidine chiral derivatives (molecular formula B, wherein R 1 It is one of hydrogen, hydroxyl, mercapto, halogen, cyano, carboxyl and sulfonic acid), and has a good effect on preventing central nervous system hypoxia and ischemic damage, and treating epilepsy. [0003] [0004] The existing methods for synthesizing 2-oxo-1-pyrrolidine chiral derivatives have problems such as difficulty in realizing industrial mass production and high production costs. Such as the synthesis of (2S)-2-((4R)-2-oxo-4-n-propyl-1-pyrrolidinyl)butanamide (also known as Buvaracetam), the paper Discovery of 4-Substituted Pyrrolidone Butanamides As New Agents with Significant Antiepileptic Activity (Journal of Medicinal Chemistry, 2004,47,530-549) discloses that when preparing Buvaracetam, a chrom...

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Problems solved by technology

[0004] The existing synthesis method of 2-oxo-1-pyrrolidine chiral derivatives has problems such as difficulty in realizing industrial mass production and high production cost

Such as the synthesis of (2S)-2-((4R)-2-oxo-4-n-propyl-1-pyrrolidinyl)butanamide (also known as Buvaracetam), the paper Discovery of 4-Substituted Pyrrolidone Butanamides As New Agents with Significant Antiepileptic Activity (Journal of Medicinal Chemistry, 2004,47,530-549) discloses that when preparing Buvaracetam, a chromatographic column is required to separate the enantiomers of Brivaracetam, which is difficult to realize mass production; the publication number is CN1882535A The patent application for invention disclosed a method for preparing 2-oxo-1-pyrrolidine derivatives. In the process of preparing buvaracetam, a chromatographic column is required to separate enantiomers, which is difficult to achieve mass production; Publication No. It is the patent document of WO2007031263, which requires two chromatographic columns to separate isomers when preparing the disclosed brivaracetam, which is difficult to realize mass production; the patent document whose publication number is WO2007065634, when the disclosed brivaracetam is prepared, needs to use To the expensive osmium metal salt, and an isomer will be produced during the preparation process, which needs to be separated by a chromatographic column, which is difficult to realize industrial production

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