第 50 卷第 5 期 Vol. 50 No. 5 2020 年 10 月 Oct 2020

所属栏目：医药及中间体 微通道反应器在匹莫范色林合成中的应用研究

魏世雄1，2，黄啟良1，车大庆2 （1. 中国农业科学院 植物保护研究所，北京 海淀 100193；2. 杭州珠联医药科技有限公司，浙江 杭州 310051）

摘　要：设计了新的匹莫范色林的合成路线，利用微通道反应器，以便宜易得的原料1-甲基-4-哌啶醇和对甲基苯磺酰氯酯化制备（1-甲基哌啶-4-基）4-甲基苯磺酸酯，然后与4-氟苄胺反应得到4-（4-氟苄基氨基）-1-甲基哌啶，再与4-异丁氧基苄胺经三光气缩合得到匹莫范色林。微通道连续流合成匹莫范色林可减少副产物，提高收率，更适合工业化生产，对农药及农药中间体的工艺优化有借鉴意义。

关键词：连续化合成；微反应器；匹莫范色林；工艺参数优化

中图分类号：R971　　文献标识码：A　　文章编号：1009-9212（2020）05-0032-05

The Application of Micro-channel Reactor in the Synthesis of Pimavanserin

WEI Shi-xiong1,2, HUANG Qi-liang1, CHE Da-qing2 (1. Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing 100193, China; 2. Hangzhou Julius Pharmaceutical Co., Ltd., Hangzhou 310051, China)

Abstract：A new synthesis route of Pimavanserin was designed and realized using microchannel reactor with cheap and commercialized materials. 1-methyl-piperidin-4-ol was reacted with 4-methylbenzene-1-sulfonyl chloride to obtain 1-methylpiperi-din-4-yl 4-methylbennesulfonate, which was then condensed with(4-fluorophenyl)methanamine to give N-(4-fluorobenzyl)-1-methylpiperidin-4-amine. Reaction of (4-isobutoxyphenyl)-methanamine and triphosgene (BTC) yielded isocyanate, which upon treatment with N-(4-fluorobenzyl)-1-methylpiperidin-4-amine to give pimavanserin. This microchannel continuous flow synthesis can reduce by-products; improve the yield; is more suitable for industrial production and has reference significance for the process optimization of pesticides and pesticide intermediates.

Key words：continuous synthesis; microchannel reactor; pimavanserin; optimization of process parameters

作者简介：魏世雄（1986—），男，甘肃会宁人，研究方向：医药及其中间体工艺开发和优化（E-mail：279475743@qq.com）。

收稿日期：2020-07-19