(2'R)-N-苯甲酰基-2'-脱氧-2'-氟-2'-甲基胞苷3',5'-二苯甲酸酯的合成工艺改进  

Improvement of the Synthesis Process of(2'R)-N-Benzoyl-2'-deoxy-2'-fluoro-2'-Methylcytidine 3',5'-dibenzoate

作　　者：王胜 程锦涛 Wang Sheng;Chen Jingtao(Zhejiang Jiangbei Pharmaceutical Co.,Ltd.,Taizhou 318000,China)

机构地区：[1]浙江江北药业有限公司,浙江台州318000

出　　处：《广东化工》2021年第17期39-39,12,共2页Guangdong Chemical Industry

摘　　要：本文对(2’R)-N-苯甲酰基-2’-脱氧-2’-氟-2’-甲基胞苷3’,5’-二苯甲酸酯的合成路线进行了改进,以(2R)-2-脱氧-2-氟-2-甲基-D-赤式戊糖酸gamma-内酯3,5-二苯甲酸酯为起始原料,经过红铝还原,氯化,胞嘧啶活化,偶合,脱保护等反应步骤合成索非布韦重要中间体(2’R)-N-苯甲酰基-2’-脱氧-2’-氟-2’-甲基胞苷3’,5’-二苯甲酸酯,同时,为了适应大生产的环保要求,增加工艺三废中的胞嘧啶和氢氧化锡的回收改进。In this paper,the synthesis route of(2’R)-N-benzoyl-2’-deoxy-2’-fluoro-2’-methyl cytidine 3’,5’-dibenzoate was improved.(2 R)-2-deoxy-2-fluoro-2-methyl-D-gamma-lactone 3,5-dibenzoate was used as the starting material,reduced by red aluminum,chlorinated,The important intermediate of sofebuvir(2’R)-N-benzoyl-2’-deoxy-2’-fluoro-2’-methyl cytosine 3’,5’-dibenzoate was synthesized by the reaction steps of activation,coupling and deprotection of cytosine.At the same time,in order to meet the environmental protection requirements of mass production,the recovery of cytosine and tin hydroxide in the third waste of the process was improved.

关 键 词：(2'R)-N-苯甲酰基-2'-脱氧-2'-氟-2'-甲基胞苷 3' 5'-二苯甲酸酯 索非布韦 胞嘧啶 磺酰氯 工艺改进 

分 类 号：TQ[化学工程]