Claims
- 1. A process, which comprises:
(a) preferentially precipitating one diastereomeric sulfonate salt of tamsulosin from a solution containing a pair of diastereomeric sulfonate salts of tamsulosin to form diastereomeric enriched precipitate and diastereomeric enriched solute.
- 2. The process according to claim 1, wherein said pair of diastereomeric sulfonate salts of tamsulosin are tamsulosin camphor-10-sulfonates.
- 3. The process according to claim 2, wherein said pair of salts are (R and S)-tamsulosin-(+)-camphor-10-sulfonate or (R and S)-tamsulosin-(−)-camphor-10-sulfonate.
- 4. The process according to claim 1, wherein said precipitation occurs spontaneously after formation of said solution of diasteromeric pairs.
- 5. The process according to claim 1, wherein said precipitation is induced.
- 6. The process according to claim 1, wherein said solution contains more of one diastereomeric salt than the other.
- 7. The process according to claim 1, which further comprises forming said solution by dissolving a solid mixture of a pair of diastereomeric sulfonate salts of tamsulosin in a solvent.
- 8. The process according to claim 7, wherein said mixture contains more of one diastereomeric salt than the other.
- 9. The process according to claim 1, which further comprises dissolving a solid mixture of (R) and (S) tamsulosin free base in a solvent and reacting said free base with a chiral sulfonic acid to form said solution containing a pair of diastereomeric sulfonate salts of tamsulosin.
- 10. The process according to claim 9, wherein said tamsulosin free base contains more (R)-tamsulosin than (S)-tamsulosin.
- 11. The process according to claim 10, wherein said mixture contains (R)- and (S)-tamsulosin within the weight ratio of 75:25 to 95:5, respectively.
- 12. The process according to claim 1, wherein said solution contains a solvent selected from the group consisting of an alcohol, water, or a mixture thereof.
- 13. The process according to claim 12, wherein said solvent is methanol and water.
- 14. The process according to claim 1, which further comprises:
(b) liberating tamsulosin free base from one of said diastereomeric enriched precipitate or solute to form optically enriched tamsulosin free base.
- 15. The process according to claim 14, which further comprises:
(c) reacting said optically enriched tamsulosin free base with a chiral sulfonic acid to form a pair of diastereomeric sulfonate salts of tamsulosin in a second solution and (d) preferentially precipitating one of said pairs from said second solution to form a diastereomeric enriched second precipitate and a diastereomeric enriched second solute.
- 16. The process according to claim 15, wherein said diasteromeric pair of tamsulosin in step (a) is the same salt as the pair in step (d).
- 17. The process according to claim 15, wherein said diastereomeric pair of tamsulosin in step (a) is a different salt than said pair in step (d).
- 18. The process according to claim 17, wherein the difference in the salts is the optical rotation of the corresponding sulfonic acid.
- 19. The process according to claim 18, wherein one diastereomeric pair is (R and S)-tamsulosin-(+)-camphor-10-sulfonate and the other is (R and S)-tamsulosin-(−)-camphor-10-sulfonate.
- 20. The process according to claim 19, wherein the diastereomeric pair in step (a) is the (R and S)-tamsulosin-(+)-camphor-10-sulfonate and the diastereomeric pair in step (d) is the (R and S)-tamsulosin-(−)-camphor-10-sulfonate.
- 21. The process according to claim 20, wherein (S)-tamsulosin-(+)-camphor-10-sulfonate is precipitated in step (a) and (R)-tamsulosin-(−)-camphor-10-sulfonate is precipitated in step (d).
- 22. The process according to claim 15, wherein the said liberation step (b) is performed on said diastereomeric enriched solute.
- 23. The process according to claim 22, wherein the diastereomer containing the (S)-tamsulosin is preferentially precipitated in step (a) and the diastereomer containing the (R)-diastereomer is preferentially precipitated in step (d).
- 24. The process according to claim 15, which further comprises:
(e) liberating tamsulosin free base from one of said diastereomeric enriched second precipitate or second solute to form optically enriched tamsulosin free base.
- 25. The process according to claim 14, which further comprises re-precipitating said enriched precipitate from a re-precipitation solvent to form a further enriched precipitate and an enriched re-precipitation solute.
- 26. The process according to claim 25, wherein said liberation step (b) liberates the tamsulosin contained in said enriched solvent and said enriched re-precipitation solvent.
- 27. The process according to claim 14, wherein said optically enriched tamsulosin free base is converted to a pharmaceutically acceptable salt thereof.
- 28. The process according to claim 27, wherein said salt is enriched (R)-tamsulosin hydrochloride.
- 29. A method of separation of enantiomers of tamsulosin by fractional crystallization comprising using a chiral camphor sulfonic acid in said crystallization.
- 30. A compound selected from the group consisting of (R)-tamsulosin-(+)-camphor-10-sulfonate, (S)-tamsulosin-(+)-camphor-10-sulfonate, (R)-tamsulosin-(−)-camphor-10-sulfonate, and (S)-tamsulosin-(−)-camphor-10-sulfonate.
- 31. The compound according to claim 30, which is (R)-tamsulosin(−)camphor-10-sulfonate
- 32. A compound according to claim 31, having at least one of the following characteristics: IR absorption peaks in KBr of 1740, 1505, 1161 and 1044 cm−1, melting range of 208-211° C. or an optical rotation of about −17.2° (c=0.5 in methanol).
- 33. A composition comprising (R) and (S) tamsulosin or the salts thereof, wherein one of said (R) or (S) forms exceeds the amount of the other within the range of 60:40 to 95:5 parts by weight.
- 34. The composition according to claim 33, wherein one of said (R) or (S) forms exceeds the amount of the other within the range of 65:35 to 95:5 parts by weight.
- 35. The composition according to claim 34, wherein said (R) and (S) tamsulosin are both in the form of the free base.
- 36. The composition according to claim 34, wherein said (R) and (S) tamsulosin are both in the form of a salt.
- 37. The composition according to claim 36, wherein said salt is a camphor-10-sulphonic acid salt of tamsulosin.
- 38. The composition according to claim 33, wherein said composition is in a solid state.
- 39. The composition according to claim 33, wherein the amount of (R) is greater than the amount of (S) in said composition.
- 40. The composition according to claim 39, wherein said amount of (R):(S) is within the range of 61:39 to 87:13 parts by weight.
- 41. The composition according to claim 40, wherein said amount of (R):(S) is within the range of 65:35 to 85:15 parts by weight.
- 42. The composition according to claim 41, wherein said amount of (R):(S) is within the range of 75:25 to 85:15 parts by weight.
- 43. The composition according to claim 41, wherein said (R) and (S) tamsulosin are tamsulosin salts.
- 44. The composition according to claim 43, wherein said (R) and (S) tamsulosin are camphor-10-sulfonic acid salts of tamsulosin.
- 45. The composition according to claim 41, wherein said (R) and (S) tamsulosin are tamsulosin free base.
- 46. The composition according to claim 34, wherein said composition is a precipitate.
- 47. The composition according to claim 41, wherein said composition is a precipitate.
- 48. The composition according to claim 44, wherein said composition is a precipitate.
- 49. A sulfonic acid addition salt of 2-(o-ethoxyphenoxy)ethylamine.
- 50. The sulfonic acid salt according to claim 49, which is 2-(o-ethoxyphenoxy)ethylamine methane sulfonate or 2-(o-ethoxyphenoxy)ethylamine tosylate.
- 51. The compound (3-aminosulfonyl-4-methoxy)phenylacetone.
- 52. Racemic tamsulosin free base in solid state.
- 53. The racemic tamsulosin according to claim 52, wherein said solid state is a precipitate.
- 54. The racemic tamsulosin according to claim 52, wherein said solid state is a crystalline form.
- 55. The racemic tamsulosin according to claim 52, wherein said racemic tamsulosin is a white or almost white microcrystalline substance.
- 56. The racemic tamsulosin according to claim 52, wherein said racemic tamsulosin is isolated racemic tamsulosin.
- 57. The racemic tamsulosin according to claim 56, wherein said racemic tamsulosin is at least 80% pure.
- 58. The racemic tamsulosin according to claim 57, wherein said racemic tamsulosin is at least 90% pure.
- 59. The racemic tamsulosin according to claim 58, wherein said racemic tamsulosin is at least 95% pure.
- 60. The racemic tamsulosin according to claim 52, which is polymorphic Form 1.
- 61. The racemic tamsulosin according to claim 52, which is polymorphic Form 2.
- 62. A process for producing racemic tamsulosin free base in solid state, which comprises precipitating racemic tamsulosin free base from a solution containing racemic tamsulosin free base in a solvent, wherein said solvent comprises at least one of water or a lower alcohol.
- 63. The process according to claim 62, wherein said solvent comprises water.
- 64. The process according to claim 62, wherein said solvent is water.
- 65. The process according to claim 64, which further comprises dissolving a racemic tamsulsoin free base residue in water to form said solution of racemic tamsulosin free base.
- 66. The process according to claim 62, wherein said solvent is a mixture of a lower alcohol and water.
- 67. The process according to claim 66, wherein said solvent is a methanol and water mixture.
- 68. The process according to claim 62, wherein said solvent comprises a lower alcohol.
- 69. The process according to claim 68, wherein said solvent is methanol.
- 70. The process according to claim 68, wherein said solvent is an ethyl acetate and methanol mixture.
- 71. The process according to claim 70, which further comprises dissolving a racemic tamsulsoin free base residue in an ethyl acetate and methanol mixture to form said solution of racemic tamsulosin free base.
- 72. The process according to claim 62, wherein said precipitation is carried out by adding water to the solution, reducing the temperature of the solution, or both.
- 73. The process according to claim 62, which futher comprises isolating said precipitated racemic tamsulosin free base.
- 74. The process according to claim 73, wherein said isolated racemic tamsulosin free base has a purity of at least 95%.
- 75. The process according to claim 62, which further comprises treating an acid addition salt of racemic tamsulosin with a base in a solvent that comprises at least one of water or a lower alcohol to form said solution of racemic tamsulosin.
- 76. The process according to claim 75, wherein said treating is carried out in methanol or a water and methanol mixture.
- 77. The process according to claim 75, which further comprises adding water concurrently with said treating with base.
- 78. The process according to claim 75, wherein said acid addition salt of tamsulosin is tamsulosin hydrochloride.
- 79. A process for isolation of tamsulosin free base, which comprises treating an acid addition salt of tamsulosin in a solvent with a base and precipitating tamsulosin free base from said solvent, wherein said solvent comprises water, a lower alcohol or both.
- 80. The process according to claim 79, wherein said solvent is a water and methanol mixture.
- 81. The process according to claim 79, wherein said acid addition salt of tamsulosin is a tamsulosin camphor-10-sulfonate salt.
- 82. The process according to claim 79, wherein said acid addition salt of tamsulosin is tamsulosin hydrochloride.
- 83. The process according to claim 79, wherein said tamsulosin free base is essentially racemic.
Parent Case Info
[0001] This application claims the benefit of priority under 35 U.S.C. § 119(e) from provisional patent application Serial No. 60/330,817, filed Oct. 31, 2001, the entire contents of which are incorporated herein by reference.
Provisional Applications (1)
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Number |
Date |
Country |
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60330817 |
Oct 2001 |
US |