左乙拉西坦中间体LV30合成工艺的开发和优化研究

Developing and Optimizing the Synthesis Technology of an Intermediate of Levetiracetam( LV30)

一种左乙拉西坦(levetiracetam)中间体LV30的制备方法,以甲苯、甲醇为溶剂、以氢化钠为甲基化试剂,调整反应条件找出最佳配比,使2-吡咯烷酮与溴丁酸甲酯反应,然后经碱水解和盐酸酸化制得LV30的外混旋体:(±)-α-乙基-(2氧-1-吡咯烷基)乙酸(LV20),LV20再通过和苯乙胺与其成盐,拆分制得左旋体(S)-α-乙基-2-氧-1-吡咯烷乙酸,-苯乙胺盐(LV30)。本发明工艺LV30收率达到40%以上,工艺简单,便于操作,产品光学纯度大于99%。

This research is about a process method of LV30,an intermediate of levetiracetam. Taking toluene and methanol as solvent,sodium hydride as methylating reagent,an optimum proportion is gained by adjusting reaction conditions. During this process,2-pyrrolidone methylation reagent reacts with methyl 2-bromobutyrate at first. Then the compound is processed through basic hydrolysis and hydrochloric acidizing to get LV20,the ex-mix optical active substance of LV30. LV30,the levo form,is obtained after LV20 is salified with phenyletheylamine and split. Applying this technology,which is simple and easy to handle,the yield of LV30 is above 35% and the optical purity of products is over 99%.