GENERAL STEPS: To a dry and clean four-necked round-bottomed flask were added (2b,3a,5a,16b,17b)-2-(4-morpholinyl)-16-(1-pyrrolidinyl)androstane-3,17-diol (50.0 g), triethylamine (47.58 mL), 4-nitrophenyl acetate (91.04 g) and dichloromethane (500 mL). The reaction mixture was heated to 80-85 °C and maintained under HPLC monitoring for 7-8 h. HPLC analysis showed that the reaction mixture contained 94-95% 17-monoacetate, 5-6% diacetate and 0.2-0.3% 3,17-diol. Upon completion of the reaction, the reaction mixture was quenched with water, followed by post-processing to isolate (2b,3a,5a,16b,17b)-17-acetoxy-3-hydroxy-2-(4-morpholinyl)-16-(1-pyrrolidinyl)androstane. The yield was 51.3 g (94.1% yield) and the HPLC purity was as follows: greater than 98% for 17-monoacetate and no more than 2.0% for diacetate. Further purification by acetonitrile crystallization gave the target product with purity greater than 99.5%.
