Synthesis of dexamethasone-4-14C

The bismethylenedioxy (BMD) derivative of dexamethasone 2 was silylated with trimethylchlorosilane and imidazole in dimethylformamide to give the 11β‐trimethylsilyloxy BMD derivative 3. The Δ1 ‐double bond in 3 was hydrogenated over 5% palladium on carbon to give the Δ4‐3‐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 14C‐methylmagnesium iodide to give an adduct 7a which on heating at reflux with lithium 2,6‐di‐t‐butylphenoxide in dioxane gave the Δ4‐3‐oxo derivative 8. Compound 8 was heated at reflux with m‐iodylbenzoic acid and diphenyl diselenide in toluene to give the Δ1,4‐3‐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‐4‐14C 10.