连续流微反应技术合成WCK 4234关键中间体  

Synthesis of key intermediate of WCK 4234 by continuous flow microreaction technology

作　　者：董江湖 王池 赵晨熙 张丹华 邓鑫浩 严琼姣 DONG Jiang-hu;WANG Chi;ZHAO Chen-xi;ZHANG Dan-hua;DENG Xin-hao;YAN Qiong-jiao(Pharmaceutical Research Institute,Wuhan Institute of Technology,Wuhan 430205,China)

机构地区：[1]武汉工程大学药物研究院,湖北武汉430205

出　　处：《化学研究与应用》2024年第4期916-920,共5页Chemical Research and Application

基　　金：湖北省重点研发计划项目(2023BCB055)资助。

摘　　要：本文应用连续流微反应技术改进新型β-内酰胺酶抑制剂WCK 4234关键中间体合成工艺,研究了溶剂、碱、温度、流速、当量比对反应的影响。实验结果表明,以(2S,5R)-6-(苄氧基)-7-氧代-1,6-二氮杂双环[3.2.1]辛烷-2-甲酰胺(Ⅱ)为原料,溶剂为二氯甲烷、碱为三乙胺、n(化合物Ⅱ):n(三氟乙酸酐):n(三乙胺)=1:2:4、温度为0℃、两个泵流速均为50μL·min^(-1)、保留时间为10 min时,目标产物的收率可达90%。优化了工艺条件,显著缩短反应时间的同时提高了反应收率,使得该技术能更好地应用于工业生产中。In this paper,the continuous flow micro-reaction technology was used to improve the synthesis process of WCK 4234 key intermediate of the novel p-lactamase inhibitor.The effects of solvent,base,temperature,flow rate and equivalence ratio on the reaction were investigated.The results showed that the solvent was dichloromethane,the base was triethylamine,n(compound I):n(trifluoroacetic anhydride):n(triethylamine)=1:2:4,the temperature was 0℃,the flow rate of the two pumps was 50μL.min',and the retention time was 10 min,the yield of the target product was up to 90%.The process conditions were optimized,the reaction time was significantly shortened and the reaction yield was increased,so that the technology could be better applied in industrial production.

关 键 词：WCK 4234 Β-内酰胺酶抑制剂 连续流 微反应 

分 类 号：O623.626[理学—有机化学]