罗非昔布的合成工艺优化  

Optimization of Synthetic Technology of Rofecoxib

作　　者：刘改枝[1] 田效志[1] 贾永艳[1] 关延彬[1] 张京玉[1] LIU Gai-zhi, TIAN Xiao-zhi, JIA Yong-yan, GUAN Yan-bin, ZHANG Jing-yu(College of Pharmacy, Henan University of Chinese Medicine, Henan Zhengzhou 450046, Chin)

机构地区：[1]河南中医药大学药学院,河南郑州450046

出　　处：《广州化工》2018年第15期45-46,60,共3页GuangZhou Chemical Industry

基　　金：河南省高等学校重点科研基金(No.16A350001)

摘　　要：对罗非昔布原料药的合成工艺进行优化,为以罗非昔布为原料的研究奠定基础。苯甲硫醚经傅克乙酰化得1-[4-(甲硫基)苯基]-乙酮(3),化合物3在冰醋酸中直接用双氧水氧化得1-[4-(甲磺酰基)苯基]-乙酮(4),无需纯化,直接以溴素溴化,最后与苯乙酸缩合、环合生成COX-2选择性抑制剂罗非昔布(1)。研究了影响每步反应的因素,包括溶剂的选择、反应温度与反应时间的考察、催化剂用量选择、后处理等,总收率为62%。The synthetic technology of rofecoxib was optimized, which laid the foundation for the study withroofecoxib as raw material. 1-（4-methylsulfanyl-phenyl） -ethanone （13） was obtained by thioanisole via Friedel craftsacetylation. Then it was oxidized with hydrogen peroxide in acetic acid to obtain 1 - （4 -methanesulfonyl - phenyl） -ethanone （ 14 ） . Without purification, it was bromized with bromine. Then it was condensed and cyclized withphenylacetic acid to generate COX-2 selective inhibitor rofecoxib （1）. Various reaction factors were studied, includingthe choice of solvent, reaction temperature and reaction time, catalyst dosage, treatment after reaction, and the overallyield was 62%.

关 键 词：罗非昔布 COX-2抑制剂 合成工艺 

分 类 号：R914.5[医药卫生—药物化学]