普瑞巴林中间体的合成

Synthesis of intermediates of pregabalin

摘要:

以异戊醛和氰基乙酸乙酯为原料，经Knoevenagel缩合、氰基加成、高温脱羧三步反应合成了普瑞巴林中间体异丁基丁二腈(III)，其中第一步和第二步反应产物分别为5-甲基-2-氰基-2-己烯酸乙酯(I)和5-甲基-2,3-二氰基己酸乙酯(II)。通过对原料配比、反应温度、反应时间等反应条件的影响进行考察和优化，I、II、III的收率分别达到92.3%、93.6%和94.2%，总收率为81.4%。各反应产物的结构通过1H NMR、IR以及MS进行了表征和确认。

Abstract:

In this study, a synthesis approach to pregabalin intermediate of isobutylsuccinonitrile(III) was proposed. Thus, III as well as 5-methyl-2-cyano-hex-2-enoic acid ethyl ester (I) and 2, 3-Dicyano-5-methyl-hexanoic acid ethyl ester (II) were synthesized from isovaleraldehyde and ethyl cyanacetate by three-step reaction of Knoevenagel Condensation, Cyano-addition and Decarboxylation. An 81.4% of overall yield was obtained by investigating molar ratio, temperature and reaction time to optimize the reaction conditions. The structures of the intermediates were characterized and confirmed by 1H NMR, IR and MS.