Synthesis of Impurity K(EP)of Fluticasone Propionate
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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