Process for the preparation of crystalline aprepitant having form I content
The present invention provides a process for preparation of crystalline aprepitant having not more than 15% by weight of Form I content which comprises, a) dissolving aprepitant in a suitable solvent to obtain a solution, b) cooling the solution to 10-15° C., c) optionally seeding the solution with aprepitant Form I crystals, d) adding an anti-solvent to the solution, and e) isolating crystalline aprepitant having not more than 15% by weight of Form I content.
1. A process for preparation of crystalline aprepitant having not more than 15% by weight of Form I content which comprises:
a) dissolving aprepitant in a suitable solvent to obtain a solution,
b) cooling the solution to 10-15° C.,
c) optionally seeding the solution with aprepitant Form I crystals,
d) adding an anti-solvent to the solution, and
e) isolating crystalline aprepitant having not more than 15% by weight of Form I content.
2. A process according to claim 1 , wherein the dissolution in step a) is carried out at a temperature ranging from about 20° C. to about 65° C.
3. A process according to claim 1 , wherein suitable solvent is selected from the group consisting of esters, lower alkanols, halogenated hydrocarbons, ketones, ethers, polar aprotic solvents or mixtures thereof.
4. A process according to claim 3 , wherein the suitable solvent is methanol.
5. A process according to claim 1 , wherein the solution obtained in step a) is initially cooled to about 30° C. to about 35° C. in about 45 minutes to about 60 minutes.
6. A process according to claim 5 , wherein the solution obtained in step a) is further cooled to 10° C. to 15° C. in about 45 minutes to about 60 minutes.
7. A process according to claim 1 , wherein the solution is seeded with aprepitant Form I crystals, prior to adding an anti-solvent.
8. A process according to claim 7 , wherein seeding is between about 0.1 and about 5% by weight of aprepitant Form I.
9. A process according to claim 1 , wherein the anti-solvent is selected from the group consisting of water, alkanes, ethers, aromatic hydrocarbon or mixtures thereof.
10. A process according to claim 8 , wherein the anti-solvent is water.
11. A process according to claim 1 , wherein the anti-solvent is pre-cooled to a temperature of about 8° C. to about 15° C.
12. A process according to claim 1 , wherein the anti-solvent is added to the solution at a temperature of 10° C. to 15° C.
13. A process according to claim 1 , wherein the anti-solvent is added to the solution at a temperature of 11° C. to 13° C.
14. A process according to claim 1 , wherein the anti-solvent is added to the solution for a time period of about 50 to about 75 minutes.