咖巴喷丁的合成研究

Study on Synthesis of Gabapentin

采用叔丁基为氮原子保护基,以重氮乙酰胺分子内C-H键插入反应为关键步骤合成了咖巴喷丁,总收率为54%。探讨了催化剂、催化剂用量对C-H键插入反应的影响及N-叔丁基-γ-内酰胺的水解体系。确定最佳工艺条件如下:醋酸铑为催化剂、其用量为0.2%、用6 mol.L-1盐酸水解。中间产物和产品结构经过IR1、HNMR1、3CNMR和HRMS表征。

The tert-butyl was used as N-protecting group,Gabapentin was synthesized via four steps with the total yield of 54% by the intramolecular C-H insertion reaction of diazoacetaraide being as the key procedure. The effect of catalyst, catalyst amount on the C- H bond insertion reaction and the effect of hydrolysis system on yield of Gabapentin were studied. The optimum conditions were as follows： dirhodium（ Ⅱ ） complex as catalyst,catalyst amount 0. 2% and 6 mol · L^-1 HCl as hydrolysis system. The structures of the intermediates and the product were determined through IR,^1HNMR,^13CNMR and HRMS.