一种酒石酸托特罗定的绿色合成方法  

A Method of Green Synthesis of Tolterodine L-tartrate

作　　者：王建军 Wang Jianjun(Guilin Pharmaceutical Co.,Ltd.,Guilin 541004,China)

机构地区：[1]桂林南药股份有限公司,广西桂林541004

出　　处：《广东化工》2021年第9期47-47,26,共2页Guangdong Chemical Industry

摘　　要：首先利用反式肉桂醇氯代制得肉桂基氯,然后其与N,N-二异丙基胺在无溶剂条件下反应制得N,N-二异丙基-3-苯基-2-丙烯基-1-胺,接着再与对甲酚进行傅-克烷基化反应制得N,N-二异丙基-3-(2-羟基-5-甲基苯基)-3-苯基丙胺,最后其经过氢溴酸成盐、L-酒石酸手性拆分成盐,得到抗尿失禁药物L-酒石酸托特罗定,总收率达到了19.9%,显著降低了该产品的工业生产成本,使其更适合于工业化生产。Firstly, chlorination of trans-cinnamyl alcohol was obtained cinnamyl chloride;then cinnamyl chloride was reacted with diisopropyl amine under solvent-free and gained the diisopropyl-(3-phenyl-allyl)-amine;furthermore, it was reacted with p-cresol by Friedel-Crafts reaction, and obtained the racemic tolterodine;finally, it was converted to hydrobromic acid salt, and got the tolterodine L-tartrate by resolution with L-tartaric acid. The total yield of the target compound was 19.9 %, The synthetic procedure reduced the cost of product, and it was more suitable for industrial manufacture.

关 键 词：酒石酸托特罗定 绿色合成 手性拆分 尿失禁 反式肉桂醇 

分 类 号：TQ[化学工程]