Beckmann rearrangement of oxime (I) in the presence of p-acetamidobenzenesulfonyl chloride and pyridine afforded acetamide (II). Subsequent fluorination of (II) using perchloryl fluoride produced fluoroenamide (III), which was hydrolyzed with HCl to give fluoroketone (IV). After treatmentof (IV) with o-phenylenephosphorochloridite (V) and pyridine, the intermediate phosphite ester (VI) was converted to iodide (VII) by means of iodine in CH2Cl2. Finally, reductive deiodination of (VI) with Zn in AcOH produced the target compound.
Dehydroepiandrosterone (VIII) was treated with o-phenylenephosphorochloridite (V) and then with iodine to afford iodide (IX), which was reduced to (X) by means of Zn and AcOH. Bromination of (X) with CuBr2 gave bromoketone (XI), and this was hydrolyzed to hydroxyketone (XII) upon treatment with aqueous NaOH in the presence of pyridine and oxygen. Subsequent treatment of (XII) with diethyl (2-chloro-1,1,2-trifluoroethyl)amine (XIII) afforded the target fluoroketone
Dehydroepiandrosterone (VIII) was first brominated with CuBr2 to give bromoketone (XIV), which was hydrolyzed to hydroxyketone (XV). After protection of (XV) as the monoacetate (XVI), fluorination at position 16 by means of (2-chloro-1,1,2-trifluoroethyl)amine (XIII) afforded fluoroketone (XVII). Ester hydrolysis in (XVI) then gave intermediate (IV).