文献类型：期刊文献

英文题名：Continuous Flow Process for the Synthesis of Betahistine via Aza-Michael-Type Reaction in Water

作者：Sun, Maolin[1,2];Yang, Jingxin[1];Fu, Youtian[1];Liang, Chaoming[1,2];Li, Hong[1];Yan, Guoming[3];Yin, Chao[3];Yu, Wei[3];Ma, Yueyue[1];Cheng, Ruihua[4];Ye, Jinxing[1,2]

机构：[1]East China Univ Sci & Technol, Engn Res Ctr Pharmaceut Proc Chem, Sch Pharm, Minist Educ, Shanghai 200237, Peoples R China;[2]Guangdong Univ Technol, Sch Biomed & Pharmaceut Sci, Guangzhou 510006, Peoples R China;[3]Shanghai Zhongxi Sunve Pharmaceut Co Ltd, Shanghai 201419, Peoples R China;[4]East China Univ Sci & Technol, Sch Chem Engn, Shanghai 200237, Peoples R China

年份：2021

卷号：25

期号：5

起止页码：1160

外文期刊名：ORGANIC PROCESS RESEARCH & DEVELOPMENT

收录：;EI(收录号：20211810307471);WOS:【SCI-EXPANDED(收录号:WOS:000656057000005)，CCR-EXPANDED(收录号:WOS:000656057000005)】；

基金：This work was partially supported by the Engineering Research Center of Pharmaceutical Process Chemistry, Ministry of Education and the Fundamental Research Funds for the Central Universities.

语种：英文

外文关键词：betahistine; continuous flow; process intensification; energy-efficient; environmentally friendly

摘要：A continuous flow process for the preparation of betahistine with a 90% isolated yield has been reported. 2Vinylpyridine and saturated methylamine hydrochloride aqueous solution were used as starting materials to achieve excellent results in the silicon carbide flow reactor, which can tolerate the corrosion of chloride ions at high temperature (170 degrees C) and pressure (25 bar). In the continuous flow process, the product can be obtained in 2.4 min with excellent conversion (>99%) and product selectivity (94%). The throughput can reach 1.06 kg h(-1), and the purity of the final product was greater than 99.9% by distillation, which were in accordance with the needs of production. This new process using environmentally friendly water as the solvent is energy-efficient, time- and cost-economic, and offers a 50% reduction in process mass intensity compared to the batch process.