丙酸氟替卡松的合成

Synthesis of Fluticasone propionate

目的合成丙酸氟替卡松。方法以氟米松(2)作为起始原料,经高碘酸氧化、丙酰化得到4;4与N,N-二甲基硫代氨基甲酰氯反应生成5;5与BrCH2Cl在K2CO3存在的条件下反应生成6;6与KF在丙酮中回流生成1。结果五步反应总收率为47.8%,产物经MS1、HNMR确证结构。结论改进后的方法避免使用对臭氧层有害且价昂的BrCH2F,收率相当。

OBJECTIVE To synthesize Fluticasone propionate. METHODS Fluticasone propionate was synthesized from Flumethasone （2） by H5106 Oxidation, Propionyl chloride acylation, and then reacted with N,N - dimethyhhiocarbamoyl chloride to get 5, 5 reacted with BrCH2Cl, and at last, using KF replace chloride with fluorine to get target product. RESULTS Chemical structure of Fluticasone propionate and its intermediate were confirmed by MS and 1 HNMR, total yield 47.8%. CONCLUSION The method improved could avoid the usage of BrCH2 F which was expensive and would destroy to the ozonosphere. The yield is corresponded to the method reported.