Patent ID: 7884222

Claim:
A process for the synthesis of tibolone (11): said process comprising the steps of: (i) protecting the 17-hydroxy group and the 3-keto group of nandrolone (1) to produce a compound of formula (3): wherein R and R 1 may be the same or different and each independently represents: C 1 to C 20 alkyl, C 6 to C 10 aryl, C 3 to C 8 cycloalkyl, C 7 to C 20 aralkyl, or C 7 to C 20 alkaryl; (ii) halogenating the carbon at the 6-position of the compound of formula (3) to produce a compound of formula (4); wherein X represents F, Cl, Br or I; (iii) dehydrohalogenating the compound of formula (4) to produce a compound of formula (5): (iv) methylating the carbon atom at the 7-position of the compound of formula (5) to produce a compound of formula (5a): (v) isomerizing the C═C double bond of the compound of formula (5a) to produce a compound of formula (6): (vi) (a) dehydrogenating at a temperature of 15° C. to 30° C. the compound of formula (6) using CuBr 2 in the presence of an alcohol, R 2 —OH to produce a product mixture comprising a compound of formula (7) and a compound of formula (7*): wherein R 2 represents C 1 to C 10 alkyl, C 6 to C 10 aryl, C 3 to C 6 cycloalkyl, C 7 to C 20 aralkyl or C 7 to C 20 alkaryl; and (b) optionally contacting the product mixture with a base; (vii) reducing the compound of formula (7) to produce a compound of formula (8): (viii) oxidizing the 17-hydroxyl group of the compound of formula (8) to produce a compound of formula (9): (ix) ethynylating the carbon at the 17-position of the compound of formula (9) to produce a compound of formula (10): (x) removing the protecting group R 2 in the compound of formula (10).