合成路线1

Methyl 3-oxoandrost-4-en-17beta-carboxylate (I) was converted to methyl 3-bromoandrosta-3,5-diene-17beta-carboxylate (II) by treatment with phosphorus tribromide in glacial acetic acid. Saponification of (II) in methanolic potassium hydroxide afforded 3-bromoandrosta-3,5-diene-17beta-carboxylic acid (III), which was further converted to 3-bromo-N-(1,1-dimethylethyl)androsta-3,5-diene-17beta-carboxamide (IV) by treatment with oxalyl chloride and quenching with tert-butylamine. Treatment of (IV) with ethyl magnesium bromide, followed by halogen metal-exchange with sec-butyllithium and gassing with carbon dioxide afforded crude epristeride (V). Alternatively, 3-bromo-N-(1,1-dimethylethyl)androsta-3,5-diene-17beta-carboxamide (IV) was prepared in one step by treatment of 17beta-androst-4-en-3-one carboxylic acid (VI) with bromomethylenedimethylammonium bromide, followed by quenching with tert-butylamine. Crude epristeride was purified and converted to the desired polymorph by heating a suspension in ethyl acetate.