依西美坦的合成工艺优化  

Improved Synthetic Process of Exemestane

作　　者：陈旺 党亚锋 刘兆鹏 CHEN Wang;DANG Yafeng;LIU Zhaopeng(School of Biological Science and Engineering,Shaanxi University of Technology,Hanzhong 723000;Hanzhong Testing and Inspection Center for Food and Drug Control,Hanzhong 723000;Key Lab.of Chemical Biology(Ministry of Education),Institute of Medicinal Chemistry,School of Pharmaceutical Sciences,Shandong University,Jinan 250012)

机构地区：[1]陕西理工大学生物科学与工程学院,陕西汉中723000 [2]汉中市食品药品检验检测中心,陕西汉中723000 [3]山东大学药学院药物化学研究所教育部天然产物化学生物学重点实验室,山东济南250012

出　　处：《中国医药工业杂志》2021年第1期56-58,共3页Chinese Journal of Pharmaceuticals

摘　　要：雄甾-4-烯-3,17-二酮(2)、原甲酸三乙酯和对甲基苯磺酸一水合物在四氢呋喃和乙醇中进行烯醇醚化反应,产物不经分离,反应液中直接加入N-甲基苯胺和37%甲醛溶液进行Mannich反应,再在酸性条件下进行消除反应,以71%的收率得到关键中间体6-亚甲基雄甾-4-烯-3,17-二酮(3)。3经钯催化的选择性1,2脱氢反应得到依西美坦(1),纯度99.46%,总收率41%(以2计)。该路线避免使用苯醌类氧化剂,简化了后续纯化过程。Androst-4-ene-3,17-dione(2)were etherified in the presence of triethyl orthoformate and p-methylbenzenesulfonic acid in tetrahydrofuran and ethanol.The product without separation,underwent the Mannich reaction with N-methylaniline and 37%formaldehyde.And then the elimination reaction under acid conditions gave the key intermediate 6-methyleneandrost-4-ene-3,17-dione(3)in a yield of 71%.Exemestane(1)was obtained by palladium catalyzed 1,2 dehydrogenation in a purity of 99.46%and a total yield of 41%(based on 2).This route avoids the use of benzoquinones oxidant,and simplifies the subsequent purification process.

关 键 词：雄甾二酮 依西美坦 钯催化脱氢 工艺优化 

分 类 号：R979.1[医药卫生—药品] R914[医药卫生—药学]