Cyproterone, 6-chloro-17|á-hydroxy-1|á,2|á-methylenpregna-4,6-dien-3,20-
dione acetate (29.2.14), is made from 17|á-hydroxyprogesterone acetate (28.3.36).
Dehydrating this using chloranyl (tetrachloro-p-benzoquinone) results in formation of an
additional double bond at position C6¨CC7 (29.2.8), and subsequent dehydration using selenium dioxide to form the corresponding divinyl ketone, 17|á-acetoxy-1,4,6-pregnatrien-
3,20-dione (29.2.9). Reacting this with diazomethane results in a 1,3-dipolar addition
reaction at C1¨CC2 of the double bond of the steroid system, which forms a derivative of
dihydropyrazole (29.2.10). This compound cleaves when reacted with chloric acid, releasing nitrogen molecules and forming a cyclopropane derivative (29.1.11). Next, the double
bond at C6¨CC7 is selectively oxidized by benzoyl peroxide, and the resulting epoxide
(29.2.12) undergoes a reaction with hydrochloric acid in acetic acid, resulting in the formation of chlorine and its subsequent dehydration, and a simultaneous opening of the cyclopropane ring, forming the compound (29.2.13). Heating this in collidine results in
intramolecular alkylation, causing cyclization into a cyclopropane ring, which forms cyproterone (29.2.14).
