罗非昔布的合成工艺优化

Optimization of Synthetic Technology of Rofecoxib

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%.