Method for the preparation of therapeutically valuable triphenylbutene derivatives
View Patent ↗The present invention concerns a method for the preparation of therapeutically valuable triphenylbutene derivatives, especially ospemifene or fispemifene.
1. A method for the preparation of a compound of formula (Ib)
wherein a compound of formula (II)
is alkylated with an alkylating reagent of the formula X—(CH 2 ) 2 —O—Pr, where X is Cl, Br, I, mesyloxy or tosyloxy, and Pr is a protecting group, to give a compound of formula (IV)
which is subjected to removal of the protecting group Pr to give the compound of formula (Ib).
2. The method according to claim 1 , wherein the compound of formula (II) is prepared by a McMurry reaction of 4-hydroxybenzophenone with 3-chloropropiophenone.
3. The method according to claim 1 or 2 , wherein the alkylation is carried out in tetrahydrofuran.
4. The method according to claim 1 , wherein the protecting group is tetrahydropyranyl.
5. The method according to claim 1 or 2 , wherein the protecting group is benzyl.
6. The method according claim 1 or 2 , wherein X in the alkylating reagent is I or Br.
7. A method for the preparation of a compound of formula (Ib)
(Ib) comprising:
wherein a compound of formula (II)
is alkylated with an alkylating reagent of the formula X—(CH 2 ) 2 —O—Pr, where X is Cl, Br, I, mesyloxy or tosyloxy, and Pr is a protecting group, to give a compound of formula (IV)
which is subjected to removal of the protecting group Pr to give the compound of formula (Ib), wherein the compound (Ib) is the Z-isomer.
8. The method of claim 7 , wherein X is I.
9. The method of claim 7 , wherein Pr is tetrahydropyranyl or benzyl.
10. The method of claim 7 , wherein Pr is 2-tetrahydropyranyl.
11. The method of claim 10 , wherein the protecting group Pr is removed using acid.
12. The method of claim 9 , wherein Pr is benzyl and is removed using zinc and acetyl chloride.