普瑞巴林的合成工艺改进及还原副产物的分离鉴定

Improved synthesis of pregabalin,separation and identification of its by-product

目的改进普瑞巴林的合成工艺并分离鉴定还原副产物。方法以亚磷酸三乙酯和氯乙酸乙酯为起始原料,经Arbuzov反应、Wittig-Horner反应、Michael加成、还原、拆分5步反应得到普瑞巴林。结果与结论目标化合物及还原副产物4-异丁基-2-吡咯烷酮经IR1、H-NMR、ESI-MS及元素分析确证,总收率为27.8%,改进后的工艺,反应步骤短,操作安全简便,有利于工业化生产。

Aim To improve the synthetic procedure of pregabalin, separate and identify the by-product. Methods Triethyl phosphite and ethyl chloroacetate were used as starting materials to synthesize pregabalin by Arbuzov reaction, Wittig-Horner reaction, Michael addition, reduction and resolution. Results and conclusion The structures of pregabalin and the by-product 4-isobutylpyrrolidin-2-one were confirmed by IR, ^1H- NMR, ESI-MS and element analysis. The overall yield is 27.8%. This process has the advantage of less steps and convenient operation, and is suitable for industrial production.