| 摘要 |
The invention relates to processes for preparing 17-alkynyl-7-hydroxy-steroids, such as 17-Ethynyl-10R,13S-dimethyl 2,3,4,7,8R,9S,10,11,12,13,14S,15,16,17-hexadecahydro-1H-cyclopenta[a]phenanthrene-3R,7R,17S-triol (also referred to as 17α-ethynyl-androst-5-ene-3β,7β,17β-triol), that are essentially free of process impurities having binding activity at nuclear estrogen receptors. |
| 主权项 |
1. A process for preparation of 17α-ethynyl-androst-5-ene-3β,7β,17β-triol essentially free of 17α-ethynyl-androst-5-ene-3β,17β-diol comprising the steps of
(a) contacting a suitably protected androst-5-en-7,17-dione having the structurewith a reducing agent to convert the ═O (ketone) functional group at position 7 to hydroxy predominately in the β-configuration;
(b) converting the oxime at position 17 in the reaction product from step (a) to the ═O (ketone) functional group; (c) converting the acyloxy group in the reaction product from step (b) to 3β-hydroxy; (d) converting the hydroxy groups at positions 3 and 7 in the product from step (c) to Me3SiO— groups; and (e) contacting the reaction product from step (d) with lithium trimethylsilyl-acetylide to introduce an ethynyl substituent at position 17 predominately in the α-configuration by addition of the acetylide to the ═O (ketone) functional group at position 17, wherein 17α-ethynyl-androst-5-ene-3β,7β,17β-triol is obtained essentially free of 17α-ethynyl-androst-5-ene-3β,17β-diol. |
