| 摘要 |
1. A process for the preparation of citalopram of formula I in which a compound of formula II wherein Z is iodo, bromo, chloro or CF3-(CF2)n-SO2-O-; and n is 0, 1, 2, 3, 4, 5, 6, 7 or 8; is subjected to a cyanide exchange reaction in which the group Z is exchanged with cyanide by reaction with a cyanide source; the resultant crude citalopram product is optionally subjected to some initial purification and the crude citalopram base is subsequently subjected to a film distillation process; the resulting citalopram product is then optionally further purified and worked up and isolated as the base or a pharmaceutically acceptable salt thereof. 2. The process of claim 1, wherein the film distillation process is short path or thin film layer distillation, preferably in thin film layer distillation. 3. The process of claim 1, wherein the crude citalopram base is dissolved in an appropriate solvent before it is subjected to film distillation. 4. The process of claims 1 to 3, wherein the distillation temperature is 200-330 degree C. and the pressure is 0.1-2.0 mmHg. 5. The process of claim 4, wherein the distillation temperature is 240-270 degree C. and the pressure is 0.6-0.8 mmHg. 6. The process of claims 1 to 5, wherein Z is bromo and the cyanide exchange reaction is carried out by reaction with cuprous cyanide in a suitable solvent. 7. The process of any one of claims 1 to 5, wherein Z is iodo, bromo, chloro or CF3-(CF2)n-SO2-O-, n is 0, 1, 2, 3, 4, 5, 6, 7 or 8, and the cyanide exchange reaction is carried out by reaction with a cyanide source in the presence of a palladium catalyst and a catalytic amount of Cu<+> or Zn<2+>. 8. The process of any one of claims 1 to 5, wherein Z is iodo, bromo, chloro or CF3-(CF2)n-SO2-O-, n is 0, 1, 2, 3, 4, 5, 6, 7 or 8, and the cyanide exchange reaction is carried out with Zn(CN)2 in the presence of a palladium catalyst. 9. The process of claim 8, wherein Z is bromo. 10. The process of any one of claims 1 to 5, wherein Z is chloro or bromo and the cyanide exchange reaction is carried out with a cyanide source in the presence of a nickel catalyst. 11. The process of claim 10, wherein Z is chloro. 12. The process of any one of claims 1 to 10, wherein the compound of formula II is S-enantiomer.
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