氟哌噻吨癸酸酯的合成  

Synthesis of Flupentixol Decanoate

作　　者：陈道鹏[1] 王圣庆 杨相平[1] 马彦琴[1] 张桂森[2] CHEN Daopeng;WANG Shengqing;YANG Xiangping;MA Yanqin;ZHANG Guisen(Jiangsu Nhwa Pharma, Corporation, Xuzhou 221116;School of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430072)

机构地区：[1]江苏恩华药业股份有限公司,江苏徐州221116 [2]华中科技大学生命科学与技术学院,湖北武汉430072

出　　处：《中国医药工业杂志》2019年第4期392-395,共4页Chinese Journal of Pharmaceuticals

摘　　要：本研究开发了一种分离(Z)-氟哌噻吨(8)的新方法。首先以2-三氟甲基-9-噻吨酮(2)为原料,依次经格氏反应、脱水和加成反应得(Z/E)-氟哌噻吨盐酸盐(6),3步收率69.6%。用氨水使6游离,再定量加入HCl/乙酸乙酯,利用(E)-氟哌噻吨盐酸盐优先成盐析出除掉(E)-异构体;然后将母液回收再成盐得(Z)-氟哌噻吨盐酸盐(7)。7再经游离、重结晶得8,纯度99.9%,2步收率29.6%。最后8和癸酰氯反应得氟哌噻吨癸酸酯,总收率15.3%(以2计)。A new method for the separation of (Z)-flupentixol (8) was developed.(Z/E)-Flupentixol hydrochloride (6) was synthesized from 2-(trifluoromethyl)-9H-thioxanthen-9-one (2) via Grignard reaction, dehydration and addition with a yield of 69.6%. Compound 6 was freed with aqueous ammonia, after quantitative addition of HCl/ ethyl acetate,(E)-flupentixol hydrochloride precipitated preferentially. The (E)-isomer was filtered out and the mother liquor was recovered and then re-salted to obtaine (Z)-flupentixol hydrochloride (7). Then 7 was subjected to dissociation and recrystallization to prepare 8 with a purity of 99.9% and a yield of 29.6%. Finally, 8 reacted with decanoyl chloride to afford flupentixol decanoate in a total yield of 15.3%(based on 2).

关 键 词：氟哌噻吨癸酸酯 精神分裂症 异构体 分离纯化 

分 类 号：R971.4[医药卫生—药品] R914.5[医药卫生—药学]