Methods for the preparation of fispemifene from ospemifene
View Patent ↗The present invention concerns a method for preparation of fispemifene by use of ospemifene as a starting material.
1. A method for the preparation of a compound of formula (I) comprising:
wherein a compound of formula (II)
is alkylated with an alkylating reagent of the formula Hal-CH 2 —COOR, wherein Hal is halogen and R is a C 1 -C 4 alkyl, to give a compound of formula (III)
and the ester of formula (III) is reduced to give the compound of formula (I).
2. The method according to claim 1 , wherein Hal is 1, Br or Cl.
3. The method according to claim 2 , wherein Hal is Br.
4. The method according to claim 1 , wherein R is ethyl.
5. The method according to claim 1 , wherein the reduction of the compound (III) is carried out by lithium aluminium hydride.
6. The method according to any of the foregoing claims, wherein the compound (I) is the Z-isomer.
7. A compound of formula (III)
wherein R is a C 1-4 -alkyl.
8. The compound according to claim 7 wherein R is methyl, ethyl, or t-butyl.
9. The compound according to claim 7 wherein R is ethyl.
10. A method for making fispemifene comprising the step of reducing a compound according to formula (III)
wherein R is C 1 -C 4 alkyl, to make fispemifene.
11. The compound according to claim 10 wherein R is methyl, ethyl, or t-butyl.
12. The method according to claim 11 , wherein R is ethyl.
13. The method according to claim 11 , wherein the reduction of the compound (III) is carried out by lithium aluminium hydride.
14. The method according to any of the claims 10 - 13 , wherein the compound (I) is the Z-isomer.