Claims
- 1. A process for the preparation of Form I of 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)-phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl-4-(3-(5-oxo-1H,4H-1,2,4-triazolo)methylmorpholine which comprises:equilibrating Form II of 2-(R)-(1-(R)-(3,5-bis(trifluoro-methyl)-phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl-4-(3-(5-oxo- 1H,4H- 1 ,2,4-triazolo)-methylmorpholine in a solvent which is selected from: ethanol, 2-propanol, acetonitrile, and isopropyl acetate; and collecting the resultant Form I of 2-(R)-(1-(R)-(3,5-bis(trifluoro-methyl)phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl-4-(3-(5-oxo-1H,4H- 1,2,4-triazolo)methylmorpholine.
- 2. A process for the preparation of Form I of 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)-phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl-4-(3-(5-oxo-1H,4H- 1,2,4-triazolo)methylmorpholine which comprises:heating a sample of 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)phenyl)-ethoxy)-3-(S)-(4-fluoro)phenyl-4-(3-(5-oxo-1H,4H- 1,2,4-triazolo)methylmorpholine of optional morphological composition to a temperature range of 215 to 230° C.; returning the sample to ambient temperature; and collecting the resultant Form I of 2-(R)-(1-(R)-(3,5-bis(trifluoro-methyl)phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl-4-(3-(5-oxo-1H,4H-1,2,4-triazolo)-methylmorpholine.
- 3. The process of claim 2 wherein the morphological composition of the starting 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)-phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl-4-(3-(5-oxo-1H,4H-1,2,4-triazolo)methylmorpholine is Form II.
- 4. A process for the preparation of Form I of 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)-phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl-4-(3-(5-oxo-1H,4H-1,2,4-triazolo)methylmorpholine which comprises:suspending 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)-phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl-4-(3-(5-oxo-1H,4H- 1,2,4-triazolo)methylmorpholine of optional morphological composition in a solution of methanol/water; adding seed crystals of Form I of 2-(R)-(1-(R)-(3,5-bis(trifluoro-methyl)phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl4-(3-(5-oxo-1H,4H-1,2,4-triazolo)methylmorpholine; stirring the resultant mixture at about 0-50° C. for a period sufficient to result in the formation of Form I of 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)-phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl-4-(3-(5-oxo-1H,4H-1,2,4-triazolo)methylmorpholine; and collecting the resultant Form I of 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)-phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl-4-(3-(5-oxo-1H,4H-1,2,4-triazolo)methylmorpholine.
- 5. The process of claim 4 wherein the morphological composition of the starting 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)-phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl-4-(3-(5-oxo-1H,4H-1,2,4-triazolo)methylmorpholine is Form II.
- 6. The process of claim 1 wherein the solvent is isopropyl acetate.
- 7. The process of claim 4 wherein the solution of methanol/watersolvent is in a ratio of 2/1 (v/v).
Parent Case Info
This is a division of application Ser. No. 09/212,511 filed Dec. 15, 1998, now U.S. Pat. No. 6,096,742, and claims benefit of Provisional No. 60/051,600 filed Jul. 2, 1997.
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Number |
Name |
Date |
Kind |
5719147 |
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Feb 1998 |
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Non-Patent Literature Citations (1)
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Provisional Applications (1)
|
Number |
Date |
Country |
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60/051600 |
Jul 1997 |
US |