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.