盐酸度洛西汀的合成工艺改进研究  

Improved method for the synthesis of duloxetine hydrochloride

作　　者：朱占群[1] 杨雪艳[1] 张俊[1] 杨先金[1] 吴范宏[1] 

机构地区：[1]华东理工大学化学与分子工程学院,结构可控先进功能材料及其制备教育部重点实验室,上海200237

出　　处：《中国新药杂志》2009年第5期447-450,共4页Chinese Journal of New Drugs

摘　　要：目的:对盐酸度洛西汀的合成工艺进行改进。方法:以2-乙酰噻吩为原料,经Mannich反应、还原、醚化、化学拆分、脱甲基、水解、氯化铵成盐等七步反应合成了目标产物,考察了每步反应的影响因素。结果:所得盐酸度洛西汀(1),HPLC纯度达99.9%,旋光+120°^+122°,总收率11.0%。结论:经优化后的合成工艺成本低廉,操作简便,适宜工业化生产。Objective： To improve the method for the synthesis of duloxetine hydrochloride.Methods： The target product was prepared from 2-acetylthiophen as the raw material,through 7-step reactions,namely Mannich reaction,reduction,etherification,chemical resolution,demethylation,hydrolysis and salt-formation with ammonium chloride.The influence factor in the process was investigated.Results： Duloxetine hydrochloride（1）,with HPLC purity of 99.9% and optical rotation of ＋120°～＋122°,was obtained,and the total yield was 11.0%.Conclusion：The optimized synthetic process may be more suitable for industrialization due to the easy operation and the lower cost.

关 键 词：盐酸度洛西汀 抗抑郁药 合成 

分 类 号：R971.43[医药卫生—药品]