Process for preparation of ospemifene

A process for the preparation of ospemifene, a compound of formula I,

• and pharmaceutically acceptable salts thereof, the process comprising:
• (a) providing an isomeric mixture of Z,E-4-(4-hydroxy-1,2-diphenylbut-1-enyl)phenol;
• (b) separating the desired Z-isomer, a compound of formula IIa, or a salt thereof and the undesired E-isomer, a compound of formula IIb, or a salt thereof from the isomeric mixture of Z,E-4-(4-hydroxy-1,2-diphenylbut-1-enyl)phenol;
• (c) recycling the undesired E-isomer, the compound of formula IIb, or a salt thereof to generate an isomeric mixture of Z,E-4-(4-hydroxy-1,2-diphenylbut-1-enyl)phenol;
• (d) optionally, repeating steps (b) and (c);
• and
• (e) converting the Z-isomer of 4-(4-hydroxy-1,2-diphenylbut-1-enyl)phenol, the compound of formula IIa, or a salt thereof obtained in step (b) to ospemifene.