文献类型：期刊文献

英文题名：Development of a Robust, Efficient, and Scalable Process for the Synthesis of Bisacodyl

作者：Bian, Wentao[1];Chen, Jiamin[1];Duan, Kongling[1];Shen, Qilei[1];Zhao, Jianhong[1]

机构：[1]East China Univ Sci & Technol, Engn Res Ctr Pharmaceut Proc Chem, Sch Pharm, Minist Educ, Shanghai 200237, Peoples R China

年份：2026

卷号：30

期号：2

起止页码：527

外文期刊名：ORGANIC PROCESS RESEARCH & DEVELOPMENT

收录：;EI(收录号：20260820146646);WOS:【SCI-EXPANDED(收录号:WOS:001684136600001)】；

基金：This research was supported by School of Pharmacy, East China University of Science and Technology.

语种：英文

外文关键词：bisacodyl; scalable synthesis; high regioselectivity; operational simplicity; single protecting group

摘要：An efficient, scalable, and chromatography-free six-step synthesis of the laxative drug bisacodyl (1) has been developed, starting from inexpensive 2-picolinic acid. This practical route achieves an overall yield of 46% and delivers the active pharmaceutical ingredient (API) in 99.88% HPLC purity. Key innovations include a crystallization-based workup for the key acid chloride intermediate, a highly selective Friedel-Crafts acylation/alkylation sequence, and a final acetylation employing a solvent-free system to suppress impurity formation. The process is distinguished by its operational simplicity, featuring direct filtration for the isolation of intermediates in five of the six steps and has been successfully demonstrated on a 500 g scale. This approach offers a robust, cost-effective, and environmentally friendly alternative to existing literature methods for the industrial manufacturing of bisacodyl.