Method for preparing substituted 3,7-dihydroxy steroids

A method to make 17α-ethynyl-androst-5-ene-3β,7β,17β-triol essentially free of steroid side-product lacking an oxygen substituent at position 7 comprising the steps of,

• (a) contacting a compound having the structure
• with a reducing agent to convert the ═O functional group at position 7 to hydroxy predominantly in the β-configuration wherein R1 is —H, C1-6 alkyl, C3-6 cycloalkyl, optionally substituted aryl or optionally substituted heteroaryl and R2 is C1-6 alkyl or aryl;
• (b) converting the ═NOR2 group at position 17 in the reaction product from step (a) to a ═O group to obtain a 7β-hydroxy-17-one compound;
• (c) converting the —OC(O)R1 group at position 3 of the 7β-hydroxy-17-one compound to a 3β-hydroxy derivative of the 7β-hydroxy-17-one compound;
• (d) converting the hydroxy groups at positions 3 and 7 in the 3β-hydroxy derivative of the 7β-hydroxy-17-one compound from step (c) to (R3)3SiO— groups, wherein each R3 independently is C1-6 alkyl or aryl;
• and
• (e) contacting the reaction product of step (d) with an compound having the structure of M-C≡C—Si(R5)3, wherein R5 independently are C1-6 alkyl or aryl and M is a Group I, Group II or transition metal, wherein 17α-ethynyl-androst-5-ene-3β,7β,17β-triol essentially free of 17α-alkynyl-androst-5-ene-3β,17β-diol is obtained.