Synthesis of dexamethasone‐4‐ 14 C

The bismethylenedioxy (BMD) derivative of dexamethasone 2 was silylated with trimethylchlorosilane and imidazole in dimethylformamide to give the 11β‐trimethylsilyloxy BMD derivative 3 . The Δ 1 ‐double bond in 3 was hydrogenated over 5% palladium on carbon to give the Δ 4 ‐3‐oxo steroid 4 . Oxidation of 4 with potassium permanganate‐sodium metaperiodate gave the seco‐acid 5 which on subsequent treatment with acetic anhydride; sodium acetate and triethylamine gave the enol‐lactone 6 . The enol‐lactone 6 was reacted with 14 C‐methylmagnesium iodide to give an adduct 7a which on heating at reflux with lithium 2,6‐di‐ t ‐butylphenoxide in dioxane gave the Δ 4 ‐3‐oxo derivative 8 . Compound 8 was heated at reflux with m ‐iodylbenzoic acid and diphenyl diselenide in toluene to give the Δ 1,4 ‐3‐oxo steroid 9 . The protecting BMD and silyl groups were removed in a single step by reaction with aqueous trifluoroacetic acid containing 2N hydrochloric acid at room temperature to give dexamethasone‐4‐ 14 C 10 .