Preparation of acid addition salts of ziprasidone and intermediates thereof by solid phase-gas phase reactions

1. A process for the preparation of an acid addition salt of ziprasidone base comprising reacting ziprasidone base in solid form with gaseous acid in a substantially dry environment thereby forming the acid addition salt of ziprasidone base, wherein the process is substantially solvent free.

2. The process of claim 1 wherein the process is solvent free.

3. The process of claim 1 further comprising agitation.

4. The process of claim 1 wherein the gaseous acid is mixed with one or more inert gases.

5. The process of claim 1 wherein reacting the ziprasidone base in sold form with gaseous acid is conducted at a temperature in the range of from about −50° C. to about 40° C.

6. The process of claim 1 wherein the acid is a hydrogen halide.

7. The process of claim 6 wherein the hydrogen halide is selected from the group consisting of hydrogen chloride and hydrogen bromide.

8. The process of claim 1 wherein the gaseous acid is an organic acid.

9. The process of claim 8 wherein the organic acid is acetic acid.

10. The process of claim 1 further comprising removal of excess acid.

11. The process of claim 10 wherein any excess gaseous acid from the process during the acid removal step is collected and recycled.

12. The process of claim 1 wherein the purity of the acid addition salt of ziprasidone base is substantially the same purity as the ziprasidone base in solid form.

13. The process of claim 1 wherein the process is conducted in a pressurized reactor.

14. The process of claim 13 wherein the reactor is maintained at a pressure of about 0.1 atm to about 3 atm.

15. The process of claim 14 wherein the pressure is about 1.0 atm to about 2.0 atm.

16. The process of claim 15 wherein the pressure is increased gradually over a period of time.

17. The process of claim 1 wherein the process is solvent free.

18. The process of claim 1 further comprising agitation.

19. The process of claim 1 wherein the gaseous acid is mixed with one or more inert gases.

20. The process of claim 1 wherein reacting the ziprasidone base in sold form with gaseous acid is conducted at a temperature in the range of from about −50° C. to about 40° C.

21. The process of claim 1 wherein the acid is a hydrogen halide.

22. The process of claim 21 wherein the hydrogen halide is selected from the group consisting of hydrogen chloride and hydrogen bromide.

23. The process of claim 1 wherein the gaseous acid is an organic acid.

24. The process of claim 23 wherein the organic acid is acetic acid.

25. The process of claim 1 further comprising removal of excess acid.

26. The process of claim 25 wherein any excess gaseous acid from the process during the acid removal step is collected and recycled.

27. The process of claim 1 wherein the purity of the acid addition salt of ziprasidone is substantially the same purity as the ziprasidone base in solid form.

28. The process of claim 1 wherein the process is conducted in a pressurized reactor.

29. The process of claim 28 wherein the reactor is maintained at a pressure of about 0.1 atm to about 3 atm.

30. The process of claim 29 wherein the pressure is about 1.0 atm to about 2.0 atm.

31. The process of claim 30 wherein the pressure is increased gradually over a period of time.

32. A process for the preparation of an acid addition salt of ziprasidone base comprising reacting ziprasidone base in solid form with gaseous acid, at a temperature in the range of from about −50° C. to about 40° C., in a substantially dry environment and agitating the ziprasidone base in solid form, thereby forming the acid addition salt of ziprasidone base, wherein the process is substantially solvent free.

33. The process of claim 32 wherein the process is solvent free.

34. The process of claim 32 wherein the acid is a hydrogen halide.

35. The process of claim 34 wherein the hydrogen halide is selected from the group consisting of hydrogen chloride and hydrogen bromide.

36. The process of claim 32 wherein the gaseous acid is an organic acid.

37. The process of claim 36 wherein the organic acid is acetic acid.

38. The process of claim 32 further comprising removal of excess acid.

39. The process of claim 38 wherein any excess gaseous acid from the process during the acid removal step is collected and recycled.

40. The process of claim 32 wherein the purity of the acid addition salt of ziprasidone base is substantially the same purity as the ziprasidone base in solid form.

41. The process of claim 32 wherein the process is conducted in a pressurized reactor.

42. The process of claim 41 wherein the reactor is maintained at a pressure of about 0.1 atm to about 3 atm.

43. The process of claim 42 wherein the pressure is about 1.0 atm to about 2.0 atm.

44. The process of claim 41 wherein the pressure is increased gradually over a period of time.

45. The process of claim 32 wherein the gaseous acid is mixed with one or more inert gases.

46. The process of claim 33 wherein the acid is a hydrogen halide.

47. The process of claim 46 wherein the hydrogen halide is selected from the group consisting of hydrogen chloride and hydrogen bromide.

48. The process of claim 33 wherein the gaseous acid is an organic acid.

49. The process of claim 48 wherein the organic acid is acetic acid.

50. The process of claim 33 wherein the purity of the acid addition salt of ziprasidone base is substantially the same purity as the ziprasidone base in solid form.

51. The process of claim 34 wherein the purity of the acid addition salt of ziprasidone base is substantially the same purity as the ziprasidone base in solid form.

52. The process of claim 35 wherein the purity of the acid addition salt of ziprasidone base is substantially the same purity as the ziprasidone base in solid form.

53. The process of claim 36 wherein the purity of the acid addition salt of ziprasidone base is substantially the same purity as the ziprasidone base in solid form.

54. The process of claim 37 wherein the purity of the acid addition salt of ziprasidone base is substantially the same purity as the ziprasidone base in solid form.

55. The process of claim 38 wherein the purity of the acid addition salt of ziprasidone base is substantially the same purity as the ziprasidone base in solid form.

56. The process of claim 46 wherein the purity of the acid addition salt of ziprasidone base is substantially the same purity as the ziprasidone base in solid form.

57. The process of claim 47 wherein the purity of the acid addition salt of ziprasidone base is substantially the same purity as the ziprasidone base in solid form.

58. The process of claim 48 wherein the purity of the acid addition salt of ziprasidone base is substantially the same purity as the ziprasidone base in solid form.

59. The process of claim 49 wherein the purity of the acid addition salt of ziprasidone base is substantially the same purity as the ziprasidone base in solid form.

60. The process of claim 33 wherein the process is conducted in a pressurized reactor at a pressure of about 1.0 atm to about 2.0 atm.

61. The process of claim 34 wherein the process is conducted in a pressurized reactor at a pressure of about 1.0 atm to about 2.0 atm.

62. The process of claim 35 wherein the process is conducted in a pressurized reactor at a pressure of about 1.0 atm to about 2.0 atm.

63. The process of claim 36 wherein the process is conducted in a pressurized reactor at a pressure of about 1.0 atm to about 2.0 atm.

64. The process of claim 37 wherein the process is conducted in a pressurized reactor at a pressure of about 1.0 atm to about 2.0 atm.

65. The process of claim 38 wherein the process is conducted in a pressurized reactor at a pressure of about 1.0 atm to about 2.0 atm.

66. The process of claim 46 wherein the process is conducted in a pressurized reactor at a pressure of about 1.0 atm to about 2.0 atm.

67. The process of claim 47 wherein the process is conducted in a pressurized reactor at a pressure of about 1.0 atm to about 2.0 atm.

68. The process of claim 48 wherein the process is conducted in a pressurized reactor at a pressure of about 1.0 atm to about 2.0 atm.

69. The process of claim 49 wherein the process is conducted in a pressurized reactor at a pressure of about 1.0 atm to about 2.0 atm.

70. The process of claim 50 wherein the process is conducted in a pressurized reactor at a pressure of about 1.0 atm to about 2.0 atm.

71. The process of claim 51 wherein the process is conducted in a pressurized reactor at a pressure of about 1.0 atm to about 2.0 atm.

72. The process of claim 52 wherein the process is conducted in a pressurized reactor at a pressure of about 1.0 atm to about 2.0 atm.

73. The process of claim 53 wherein the process is conducted in a pressurized reactor at a pressure of about 1.0 atm to about 2.0 atm.

74. The process of claim 54 wherein the process is conducted in a pressurized reactor at a pressure of about 1.0 atm to about 2.0 atm.

75. The process of claim 55 wherein the process is conducted in a pressurized reactor at a pressure of about 1.0 atm to about 2.0 atm.

76. The process of claim 56 wherein the process is conducted in a pressurized reactor at a pressure of about 1.0 atm to about 2.0 atm.

77. The process of claim 57 wherein the process is conducted in a pressurized reactor at a pressure of about 1.0 atm to about 2.0 atm.

78. The process of claim 58 wherein the process is conducted in a pressurized reactor at a pressure of about 1.0 atm to about 2.0 atm.

79. The process of claim 59 wherein the process is conducted in a pressurized reactor at a pressure of about 1.0 atm to about 2.0 atm.