Process for the preparation of Citalopram intermediate
View Patent ↗The present invention provides, inter alia, a novel process for the preparation of Citalopram, a known antidepressant.
1. A method for preparing a salt of the compound of Formula III having the following structure:
said method comprising:
(a) contacting a compound of Formula I having the following structure:
with 4-fluorophenyl magnesium bromide to form an intermediate of Formula II having the following structure:
(b)contacting said intermediate of Formula II with dimethylaminopropyl magnesium chloride in an organic solvent to form a reaction mixture; and
(c) quenching said reaction mixture with an acid to form a product mixture comprising said salt of the compound of Formula III.
2. The method of claim 1 , wherein said salt of the compound of Formula II is an acid salt.
3. The method of claim 2 , wherein said acid salt is a member selected from the group consisting of a HCl salt, a HBr salt, a H 2 SO 4 salt, a H 3 PO 4 salt, a methanesulfonic acid salt, a trifluoroacetic acid salt, an acetic acid salt, a fumaric acid salt and a citric acid salt.
4. The method of claim 1 , wherein said organic solvent in step (b) is a member selected from the group consisting of diethylether, t-butylmethylether, THF, dioxane, toluene, xylene and mixtures thereof.
5. The method of claim 1 , wherein said organic solvent in step (b) is a mixture of THF and toluene.
6. The method of claim 1 , wherein said acid in step (c) is a member selected from the group consisting of HCl, HBr, H 2 SO 4 , H 3 PO 4 , methanesulfonic acid, trifluoroacetic acid, acetic acid, fuinaric acid and citric acid.
7. The method of claim 1 , wherein said acid is aqueous HCl.
8. The method of claim 1 further comprising:
(d) isolating said salt of the compound of Formula III from said product mixture.
9. The method of claim 8 , wherein step (d) comprises:
(i) filtering said product mixture to obtain said salt of the compound of Formula III.
10. The method of claim 9 , wherein step (d) further comprises:
(ii) washing said salt of the compound of Fonnula III with water and toluene.
11. The method of claim 10 , wherein step (d) further comprises:
(iii) recrystallizing said salt of the compound of Formula III from a member selected from the group consisting of 1-butanol, 2-butanol and water.
12. The method of claim 11 , wherein step (d) further comprises:
(iv) recrystallizing said salt of the compound of Formula III from 2-butanol.