正交法优选1-氨甲基-1，2，3，4-四氢异喹啉盐酸盐的合成工艺条件

Optimization of synthetic technological conditions for 1-aminomethyl-1，2，3，4-tetrahydroisoquinoline hydrochloride with orthogonal design

摘要:

目的：利用正交实验法优选药物重要中间体1-氨甲基-1，2，3，4-四氢异喹啉盐酸盐（1）的合成工艺条件。方法：采用正交实验方法，考察合成（1）中的酰化、邻苯二甲酰亚胺N-烃化、Bischler-Napieralski反应、肼解与还原等主要反应的关键条件对收率的影响，筛选出主要反应的优选实验条件。结果：合成（1）的总收率达到了62.4%，约为原来总收率的2.5倍。结论：该合成工艺路线具有原料廉价易得、反应操作简便、兼顾环保以及产品收率高且品质好等优点；具有较好的工业化生产前景。

Abstract:

Objective：To optimize the synthetic technological conditions of 1-aminomethyl-1，2，3，4-tetrahydroisoquinoline hy－drochloride as important intermediate for drugs by orthogonal experimental method. Methods：The target product was synthesized from β-phenethylamine by phthalimide N-hydrocarbylation reaction，Bischler-Napieralski reaction，cyclization with Bischler-Napieralski method，hydrazinolysis reaction，reduction and salification. The key factors on each reaction were discussed separately and optimized by orthogonal experiment. Results：The overall yield was 65%，2.5 times as much as that of the reported. Conclusion: The optimized synthetic route has promise in industrial production for its cheap and readily available raw materials，easy and environmentally-friend processes，high yield and good quality of products.