Process for the preparation of oxcarbazepine
The present invention relates to an improved process for the preparation of 10-oxo-10,11-dihydro-5H-dibenz[b,f]azepine-5-carboxamide (Oxcarbazepine) by reacting 10-methoxy-5H-dibenz[b,f]azepine (10-methoxyiminostilbene) and alkali metal cyanate in presence of α-hydroxy acids, and also relates to the process for the preparation of carbamazepine from iminostilbene. Further the present invention is directed to the novel crystalline form of 10-methoxy carbamazepine.
1. A process for the preparation of Oxcarbazepine which comprises the steps of:
(a) reacting 10-methoxy iminostilbene with an alkali metal cyanate and an α-hydroxy acid in a solvent;
(b) isolating 10-methoxy carbamazepine;
(c) optionally crystallizing 10-methoxy carbamazepine;
(d) hydrolyzing of 10-methoxy carbamazepine in the presence of an acid and a solvent; and
(e) isolating Oxcarbazepine.
2. A process for the preparation of Carbamazepine, which comprises the steps of:
(a) reacting iminostilbene with an alkali metal cyanate and an α-hydroxy acid in a solvent;
(b) isolating Carbamazepine; and
(c) optionally crystallizing to give pure Carbamazepine.
3. The process according to claim 1 or claim 2 , wherein the alkali metal cyanate is selected from the group consisting of sodium cyanate and potassium cyanate.
4. The process according to claim 1 or claim 2 , wherein the α-hydroxy acid is selected from the group consisting of glycolic acid, lactic acid, citric acid, tartaric acid, mandelic acid and mixtures thereof.
5. The process according to claim 1 or claim 2 , wherein the solvent of step (a) is selected from the group consisting of dichloromethane, dichloroethane, toluene, hexane, heptanes, and cyclohexane.
6. The process according to claim 1 , wherein the crystallization of step (c) is carried out with a solvent selected from the group consisting of methanol, ethanol, isopropyl alcohol and mixtures thereof.
7. The process according to claim 1 , wherein the acid of step (d) is an organic acid.
8. The process according to claim 1 , wherein the solvent of step (d) is selected from the group consisting of water, a water miscible organic solvent, a water immiscible organic solvent and mixtures thereof.
9. The process according to claim 8 , wherein the water miscible organic solvent is selected from the group consisting of methanol, ethanol, propanol, isopropanol, butanol, t-butanol, tetrahydrofuran (THF), dimethylformamide (DMF), dimethylsulfoxide (DMSO), acetonitrile and mixtures thereof and the water immiscible organic solvent is selected from the group consisting of benzene, hexane, toluene, methylene dichloride, ethylene dichloride, chloroform, cyclohexane, xylene and mixtures thereof.
10. Crystalline 10-methoxy carbamazepine having an X-ray powder diffraction pattern characterized by peaks at 10.37, 10.54, 11.31, 12.88, 14.64, 19.19, 19.53, 20.60, 21.78, 22.84, 23.46, 26.47 and 27.47±0.2 2θ values.
11. The crystalline 10-methoxy carbamazepine according to claim 10 having a substantially similar X-ray powder diffraction pattern as depicted in FIG. 1 .
12. A process for the preparation of Oxcarbazepine comprising the utilization of the crystalline 10-methoxy carbamazepine according to claim 10 or claim 11 .
13. The process according to claim 7 , wherein the organic acid is selected from the group consisting of oxalic acid and formic acid.