第七讲精细有机合成工艺优化及其RD1.ppt

精细有机合成工艺优化;—Sir John Cornforth “The ideal chemical process is that which a one-armed operator can perform by pouring the reactants into a bath tub and collecting pure product from the drain hole.” ;苦味酸的制备路线;单元反应优化---动力学路径;基本概念;副反应;相对速度;单元反应优化;单元反应优化;实验测定;单元反应优化;单元反应优化;单元反应优化;单元反应优化;单元反应优化;实例分析 (一);平行副反应;该主/平行副反应的浓度效应不显著;温度效应;浓度效应;结 果;实例分析 (二);T = 120oC, S* ~ P/S = Ap/As (GC)= 0 T = 150oC, S* ~ P/S = Ap/As (GC) = 10;CCN;结论;工艺路线优化;一锅反应法;前一步原料、辅剂、副产物对后面各步反应没有负作用。 各步反应使用溶剂相同。 各步反应操作设备相同。;溶剂归一化;纯化过程简并; Strategy for Process Development ?Steal the best from the Synthesis Chemists ?Review all the past history ?Develop a workable interim synthesis ?Search for a real chemical process ;Synthesis Process Research;Discovery Chemistry Synthesis;Benzaldehyde Synthesis;Amino Acid Synthesis;First Scalable Synthesis: Ugi-Resolution Route;What About Aminoalkylations?;Scope;3 steps 63% yield;Asymmetric Petasis;Asymmetric Hydrogenation;Asymmetric Hydrogenation;头孢中间体的合成工艺研发 生产工艺安全性;The Medicinal Synthesis;The Medicinal Synthesis ?Long and Complex ?Unstable species throughout ?Run on a 2g of penultimate intermediate –produced 0.5 g of product ?Run on a 10g of penultimate intermediate –produced 0.5 g of product ;SYNTHESIS OF THE SIDE CHAIN