In order to control the quality of fluticasone propionate,the synthesis route of impurity K(1)in EP of fluticasone propionate was designed.An economical and available starting material,dexamethasone(2),was acylated,chlorinated,hydrolyzed and deacetylated to obtain 6α-chloro-9α-fluoro-11β,17α,21-trihydroxy-16α-methyl-androstane-1,4-diene-3,20-dione(5).Then 5 was oxidized by periodic acid followed by the substitution with propionyl chloride to obtain 6α-chloro-9α-fluoro-1 1β-hydroxy-16α-methyl-17α-propoyloxy-3-oxandrostane-1,4-diene-17β-carboxylic acid(7).Then 7 underwent the rearrangement acylation reaction with N,N-dimethylthioformyl chloride,and then was hydrolyzed under alkaline conditions to obtain 6α-chloro-9α-fluoro-11β-hydroxy-16α-methyl-17α-propoyloxy-3-oxandrostane-1,4-diene-17β-carbothioic acid(9).Finally,the target product 1 was obtained by substituting 9 with bromofluoromethane under alkaline conditions.The total yield was about 48.34％(based on 2)with the purity more than 99％.This synthetic route of 1 was reported at the first time,which had certain reference significance for the synthesis of fluticasone propionate.
fluticasone propionate impurity Kfluticasone propionatesynthesis processquality control
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