【摘要】 异戊醛和氰乙酸乙酯缩合,与丙二酸二乙酯加成,盐酸水解脱羧得到重要中间体3-异丁基戊二酸;首次提纯得到3-异丁基戊二酸纯品,经环合、氨解得到3-氨甲酰甲基-5-甲基己酸,重排得到普瑞巴林外消旋体.使用新型拆分剂对甲苯磺酰胺基-D-苯甘氨酸拆分普瑞巴林外消旋体的拆分率为40%.经过合成工艺和拆分工艺的开发与优化,得出较优的反应条件,能有效降低普瑞巴林的生产成本,更适合S-普瑞巴林的工业化生产.更多还原

【Abstract】 The 3-isobutylglutaric acid was synthesized from isovaleraldehyde reacted with ethyl cyanoacetate and diethyl malonate,then hydrolysis and decarboxylation.Pure 3-isobutylglutaric acid was obtained by purification.3-carbamoylmethyl-5-methylhexanoic acid could be obtained by 3-isobutylglutaric acid via cyclization and ammonolysis reaction.Finally,3-aminomethyl-5-methylhexanoic acid was obtained from 3-carbamoylmethyl-5-methylhexanoic acid.A new chiral resolution agent of(4-methyl phenyl sulfonyl)amino-D-benzeneacetic acid was disclosed to obtain S-pregabalin.The yield was 40%.After investigation of a series of synthetic routes of S-pregabalin,the best synthetic processes had been determined which was suitable for scale production with the lower production cost.更多还原