IP Library › Granted Patent US 6,992,211
Granted Patent B2
US 6,992,211 · App. 10/480,427 · Granted Jan 31, 2006

Crystalline form of phenylethanolamine, the preparation thereof and pharmaceutical compositions comprising the same

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Quick Facts
Patent No.
US 6,992,211
App. No.
10/480,427
Granted
Jan 31, 2006
Kind
B2
Abstract

The subject-matter of the invention is the B form of ethyl [(7S)-7-[(2R)-2-(3-chlorophenyl)-2-hydroxyethylamino]-5,6,7,8-tetrahydronaphth-2-yloxy]acetate hydrochloride, of use as a medicament, which exhibits in particular the following physical characteristics: characteristic IR absorption peaks (cm −1 ): 2780, 2736, 1722, 1211; melting point: 129+/−2° C.; characteristic lines of the powder X-ray diffraction diagram (to within 0.1(2θ)): 7.69, 9.83, 13.95, 16.58, 18.70, 20.40, 21.57, 23.40, 24.15 and 25.64. The product can be obtained by salification of the base or recrystallization of the salt from an alcohol.

Claims (27)

1. B form of ethyl [(7S)-7-[(2R)-2-(3-chlorophenyl)-2-hydroxyethylamino]-5,6,7,8-tetrahydronaphth-2-yloxy]acetate hydrochloride, the infrared spectrum of which exhibits the following characteristic absorption peaks: 2780, 2736, 1722, 1211 cm −1 .

2. B form of ethyl [(7S)-7-[(2R)-2-(3-chlorophenyl)-2-hydroxyethylamino]-5,6,7,8-tetrahydronaphth-2-yloxy]acetate hydrochloride according to claim 1 having a melting point of 129+/−2° C., determined by differential scanning calorimetry.

3. B form of ethyl [(7S)-7-[(2R)-2-(3-chlorophenyl)-2-hydroxyethylamino]-5,6,7,8-tetrahydronaphth-2-yloxy]acetate hydrochloride according to claim 1 , the powder X-ray diffraction diagram of which exhibits the following characteristic lines: 7.69, 9.83, 13.95, 16.58, 18.70, 20.40, 21.57, 23.40, 24.15 and 25.64.

4. Process for the preparation of the compound according to claim 1 wherein a solution of concentrated HCl is added to a solution of ethyl [(7S)-7-[(2R)-2-(3-chlorophenyl)-2-hydroxyethylamino]-5,6,7,8-tetrahydronaphth-2-yloxy]acetate in a solvent chosen from propan-2-ol, 2-methylpropan-2-ol and butan-2-ol at a temperature ranging from 40 to 70° C., crystallization is initiated by seeding with a small amount of the B form and then the solution is gradually cooled.

5. Process according to claim 4 wherein the crystallization is carried out at a temperature of 50 to 70° C.

6. Process according to claim 4 wherein the solvent is propan-2-ol.

7. Process for the preparation of the compound according to claim 1 wherein ethyl [(7S)-7-[(2R)-2-(3-chlorophenyl)-2-hydroxyethylamino]-5,6,7,8-tetrahydronaphth-2-yloxy]acetate hydrochloride is suspended in propan-2-ol, 2-methylpropan-2-ol and butan-2-ol at a temperature ranging from ambient temperature to 70° C. and the suspension is maintained under isothermal conditions until the crystals have been converted to the B form.

8. Process for the preparation of the compound according to claim 1 wherein a solution of ethyl [(7S)-7-[(2R)-2-(3-chlorophenyl)-2-hydroxyethylamino]-5,6,7,8-tetrahydronaphth-2-yloxy]acetate hydrochloride in an organic solvent chosen from an alcohol or a ketone is heated to a temperature of 45 to 70° C., the solution is concentrated by evaporation or distillation and then the solution is gradually cooled with stirring to a temperature of 10 to 40° C.

9. Process according to claim 8 wherein the solvent is propan-2-ol.

10. Pharmaceutical composition, comprising the compound according to claim 1 as active principle and one or more pharmaceutically acceptable excipients.

11. Process for the preparation of the compound according to claim 2 wherein a solution of concentrated HCl is added to a solution of ethyl [(7S)-7-[(2R)-2-(3-chlorophenyl)-2-hydroxyethylamino]-5,6,7,8-tetrahydronaphth-2-yloxy]acetate in a solvent chosen from propan-2-ol, 2-methylpropan-2-ol and butan-2-ol at a temperature ranging from 40 to 70° C., crystallization is initiated by seeding with a small amount of the B form and then the solution is gradually cooled.

12. Process for the preparation of the compound according to claim 3 wherein a solution of concentrated HCl is added to a solution of ethyl [(7S)-7-[(2R)-2-(3-chlorophenyl)-2-hydroxyethylamino]-5,6,7,8-tetrahydronaphth-2-yloxy]acetate in a solvent chosen from propan-2-ol, 2-methylpropan-2-ol and butan-2-ol at a temperature ranging from 40 to 70° C., crystallization is initiated by seeding with a small amount of the B form and then the solution is gradually cooled.

13. Process according to claim 11 wherein the crystallization is carried out at a temperature of 50 to 70° C.

14. Process according to claim 11 wherein the crystallization is carried out at a temperature of 50 to 70° C.

15. Process according to claim 11 wherein the solvent is propan-2-ol.

16. Process according to claim 12 wherein the solvent is propan-2-ol.

17. Process according to claim 5 wherein the solvent is propan-2-ol.

18. Process according to claim 13 wherein the solvent is propan-2-ol.

19. Process according to claim 14 wherein the solvent is propan-2-ol.

20. Process for the preparation of the compound according to claim 2 wherein ethyl [(7S)-7-[(2R)-2-(3-chlorophenyl)-2-hydroxyethylamino]-5,6,7,8-tetrahydronaphth-2-yloxy]acetate hydrochloride is suspended in propan-2-ol, 2-methylpropan-2-ol and butan-2-ol at a temperature ranging from ambient temperature to 70° C. and the suspension is maintained under isothermal conditions until the crystals have been converted to the B form.

21. Process for the preparation of the compound according to claim 3 wherein ethyl [(7S)-7-[(2R)-2-(3-chlorophenyl)-2-hydroxyethylamino]-5,6,7,8-tetrahydronaphth-2-yloxy]acetate hydrochloride is suspended in propan-2-ol, 2-methylpropan-2-ol and butan-2-ol at a temperature ranging from ambient temperature to 70° C. and the suspension is maintained under isothermal conditions until the crystals have been converted to the B form.

22. Process for the preparation of the compound according to claim 2 wherein a solution of ethyl [(7S)-7-[(2R)-2-(3-chlorophenyl)-2-hydroxyethylamino]-5,6,7,8-tetrahydronaphth-2-yloxy]acetate hydrochloride in an organic solvent chosen from an alcohol or a ketone is heated to a temperature of 45 to 70° C., the solution is concentrated by evaporation or distillation and then the solution is gradually cooled with stirring to a temperature of 10 to 40° C.

23. Process for the preparation of the compound according to claim 3 wherein a solution of ethyl [(7S)-7-[(2R)-2-(3-chlorophenyl)-2-hydroxyethylamino]-5,6,7,8-tetrahydronaphth-2-yloxy]acetate hydrochloride in an organic solvent chosen from an alcohol or a ketone is heated to a temperature of 45 to 70° C., the solution is concentrated by evaporation or distillation and then the solution is gradually cooled with stirring to a temperature of 10 to 40° C.

24. Process according to claim 5 wherein the solvent is propan-2-ol.

25. Process according to claim 5 wherein the solvent is propan-2-ol.

26. Pharmaceutical composition, comprising the compound according to claim 2 as active principle and one or more pharmaceutically acceptable excipients.

27. Pharmaceutical composition, comprising the compound according to claim 3 as active principle and one or more pharmaceutically acceptable excipients.