2015.4张霁博士—叠缩方法绿色化工艺化学.pdf

Greening the Process Chemistry by Telescoping 叠缩方法绿色化工艺化学 Dr. Ji Zhang (张霁博士) HEC Pharma (东阳光药业) ISPE China Annual Spring Conference 2015 Beijing, China Process of Midazolam by Telescoping 合成工艺实例 叠缩工艺 Telescoping process (Telescoped or telescopic process) 是直接将未经纯化后处理的粗产物投入下一步反应，经 过数步免除纯化过程（用符号[ ]表示）后才经分离纯 化而获取高纯度的产物。 The crude product was directly treated into the next reaction without purification, a process that eliminating purification steps (indicated by symbol [ ] represents) and finally isolation and purification to obtain a high purity product. A + B I1 Ix P 叠缩工艺和一锅法反应 (Telescoping and one-pot reaction  数步反应的简化;  强调反应的简单性，  避开一些中间体的分离  即把多步反应按顺序或 纯化; 者一次性投料在一个反应器  工艺过程的简捷和快速途 里得到所需的产物，而不牵 径 涉到后处理纯化过程 simplify the number of Emphasizes simplicity steps The multi-step reaction Avoid separations of some VS sequence or a one-pot in a intermediates reactor, without involving Simple and fast way for post-treatment purification process process 叠缩工艺 一锅法反应 (Telescoping process ) （One-pot reaction） 叠缩工艺和一锅法反应 (Telescoping and One-pot reaction) 1 理想的工艺路线设计应使所有中间体无需 经过柱层析纯化 Ideal process should be designed so that all intermediate without purification by column chromatography 2 叠缩工艺就是将多步工艺过程免 经过溶解、过滤、打浆