Synthesis of fluorinated 3β-hydroxypregn-5-en-20-one derivatives

Treatment of the unstable 3β-hydroxy-20, 20-dimethoxypregn-5-ene 3-acetate with acetic anhydride at reflux temperature gave a mixture of 3β-hydroxy-20-methoxypregna-5, 17(20)-diene and 3β-hydroxy-20-methoxypregna-5, 20-diene 3-acetates. Fluorination of this mixture with perchloryl fluoride afforded after fractionated crystallization 3β-hydroxy-17-fluoro-20-methoxypregna-5, 20-diene 3-acetate. Acid hydrolysis of the reaction mixture and subsequent Chromatographic separation led to 3β-hydroxy-17-fluoropregn-5-en-20-one 3-acetate and 3β-hydroxy-21-fluoropregn-5-en-20-one 3-acetate. 3β-Hydroxy-17-fluoro-20-methoxypregna-5, 20-diene 3-acetate did not react further with perchloryl fluoride even under forcing conditions. Fluorination of 3β-hydroxy-20-(N-ethyl benzylamino)-pregna-5, 17(20)-diene gave 3β-hydroxy-17, 21-difluoro-pregn-5-en-20-one, exclusively.