Heptafluoro-p-tolyl as a protecting group in a synthesis of 3-hydroxy-17a-aza-17a-homopregn-5-en-20-one. A potential inhibitor of androgen biosynthesis

Abstract

A synthesis of 3-hydroxy-17a-aza-17a-homopregn-5-en-20-one 1 using perfluorotolyl as protecting group for the hydroxy function is described. The phase-transfer-catalysed reaction of octafluorotoluene with dehydroepiandrosterone gave the perfluorotolyl ether 3. Beckmann rearrangement of its (E)-oxime 4 gave the lactam 6. This reacted with methyl trifluoromethanesulphonate to give the lactam methyl ether which was reduced by sodium borohydride to the protected 17-aza-17a-homosteroid amine 8. Acetylation followed by cleavage of the perfluorotolyl group using sodium methoxide in dimethylformamide gave 1 in 15% overall yield.