醋酸可的松的合成工艺研究  

Study on Synthetic Process of Cortisone Acetate

作　　者：刘风强 邹义勇 陈小艳 陈思宇 LIU Fengqiang;ZOU Yiyong;CHEN Xiaoyan;CHEN Siyu(Taizhou Xianju Pharmaceutical Co.,Ltd.,Taizhou,Zhejiang 317016,China)

机构地区：[1]台州仙琚药业有限公司,浙江台州317016

出　　处：《浙江化工》2025年第2期26-30,共5页Zhejiang Chemical Industry

摘　　要：针对传统醋酸可的松合成工艺中涉及的卤代试剂用量大、设备腐蚀严重及工艺成本高等问题,本研究以氰醇化物4-烯-孕甾-17α-氰基-17β-氯甲基(二甲基硅基)-3,11-二酮为原料,经强碱二异丙基氨基锂(LDA)引发的分子内环合-水解实现α-卤代酮骨架的构建,并经后续与醋酸钾的亲核取代反应制备得到醋酸可的松,总收率达85.5%。本方法避免了传统工艺中成本高、污染严重试剂单质碘的使用,具有反应步骤短、产物易分离、收率高等特点,产物结构经^(1)H NMR、^(13)C NMR及HRMS确证。In order to solve the problems of large amount of halogenated reagents,serious equipment corrosion and high process cost involved in the traditional cortisone acetate synthesis process,this study used cyanoethanol 4-ene-pregn-17α-cyano-17β-chloromethyl(dimethylsilyl)-3,11-dione as the raw material,and constructd theα-halogenated ketone skeleton through intramolecular cyclization-hydrolysis induced by strong base lithium diisopropylamide(LDA).Cortisone acetate was prepared by subsequent nucleophilic substitution reaction with potassium acetate,with a total yield of 85.5%.This method avoids the use of elemental iodine in the traditional process with high cost and serious pollution,and has the characteristics of short reaction steps,easy separation of products,high yield,and the product structure is confirmed by ^(1)H NMR,^(13)C NMR and HRMS.

关 键 词：醋酸可的松 环合 水解 亲核取代 合成工艺 

分 类 号：TQ460.31[化学工程—制药化工]