Synthesis of steroidal cyclophosphamides

The Reformatsky product of estrone methyl ether and ethyl bromo-acetate was transformed by two separate routes to 21-amino-3-methoxy-17alpha-pregna-1,3,5(10)-trien-17beta-ol (9). Cyclization with bis- (2-chloroethyl) phosphoramide dichloride produced the steroidal cyclophosphamide 10. Analogous syntheses transformed androstenolone into steroidal cyclophosphamide 20 and androstenedione into steroidal cyclophosphamide 28.