恩替卡韦关键中间体4-甲氧苯基二苯基氯甲烷的合成工艺研究  

Synthesis of Key Intermediate 4-Methoxytriphenylchloromethane of Entecavir

作　　者：刘志 程天星 卓长城 刘子畅 程青芳 LIU Zhi;CHENG Tian-xing;ZHUO Chang-cheng;LIU Zi-chang;CHENG Qing-fang(Lianyungang Guike Pharmaceutical Co.,Ltd.,lianyungang 222000;School of Pharmacy,Jiangsu Ocean University,Lianyungang 222005,China;Department of chemistry,University of Melbourne,Melbourne VIC3010,Australia)

机构地区：[1]连云港贵科药业有限公司,江苏连云港222000 [2]江苏海洋大学药学院,江苏连云港222005 [3]墨尔本大学化学系,澳大利亚墨尔本VIC3010

出　　处：《精细化工中间体》2021年第1期11-14,共4页Fine Chemical Intermediates

基　　金：连云港高新区科技计划项目(ZD201917)。

摘　　要：以苯(2)为原料,与四氯化碳发生傅-克烷基化反应,制得二苯基二氯甲烷(3),优化条件下收率84.7%;3和苯甲醚再发生傅-克烷基化反应,得到恩替卡韦关键中间体4-甲氧苯基二苯基氯甲烷(1),优化条件下收率85.9%,产品纯度99.1%。考察了催化剂的结构、催化剂的量、反应温度等因素对收率的影响。通过^(1)H NMR、^(13)C NMR和ESI-MS确证了1及中间体的结构。Dichlorodiphenylmethane(3)was obtained from benzene(2)and carbon tetrachloride through FriedelCrafts alkylation with a yield of 84.7%.Then 4-methoxytriphenylchloromethane(1)was synthesized from 3 and anisole through Friedel-Crafts alkylation with a yield of 85.9%and a chromatographic purity of 99.1%.The affecting factors including the structure,ratio of the catalysts,and the reaction temperature were investigated.The structures of the compound 1 and intermediate were characterized by ^(1)H NMR,^(13)C NMR and ESI-MS.

关 键 词：恩替卡韦 4-甲氧苯基二苯基氯甲烷 傅-克烷基化反应 

分 类 号：TQ31[化学工程—高聚物工业]