Acetic Anhydride → 3beta-Acetoxy-9alpha-fluoro-17alpha-hydroxy-16beta-methyl-5alpha-pregnan-20-one

Participants

Reaction Steps

3β-Acetoxy-17α-hydroxy-16β-methyl-5α-pregnan-20-one (1g, prepared by treatment of the corresponding 3β-ol with acetic anhydride in pyridine) was dissolved in fluorotrichloromethane (250 ml) and chloroform (200 ml) containing sodium trifluoroacetate (ca. 2g) and sodium fluoride (ca. 2g). The resulting solution was cooled to -78° and vigourously stirred, whereupon fluorine from four 750 cc bottles (8-10% v/v fluorine in nitrogen) was added over 9-10 hours. The reaction solution was then poured into aqueous sodium thiosulphate and the organic layer was separated, washed with water, dried over potassium carbonate and evaporated to dryness. The residue was purified by liquid chromatography, eluting with cyclohexane containing 30% v/v ethyl acetate and 0.1% v/v pyridine, to yield 3β-acetoxy-9α-fluoro-17α-hydroxy-16β-methyl-5α-pregnan-20-one (50%); m.p. 150° (after recrystallisation from acetone); PMR spectrum includes signals at δ 2.20 (21-Me), 2.00 (3-0.CO.CH3), 0.92 (19-Me) and 0.87 (18-Me); FMR φ* + 179.5 ppm. (Found: C, 70.51; H, 9.20; F, 4.48; C24H37FO4 requires C, 70.55; H, 9.13; F, 4.65%).

Provenance & Evidence