Selective n-sulfonylation of 2-amino flouro-and trifluoroalkyl substituted alcohols

Abstract

Processes for preparing sulfonamide trifluoroalkyl substituted alcohol compounds are provided. Desirably, the compounds are heterocyclic sulfonamide trifluoroalkyl substituted alcohol compounds or phenyl sulfonamide trifluoroalkyl substituted alcohol compounds.

Description

Claims

1. A process for preparing a sulfonamide trifluoroalkyl substituted alcohol of the structure:

2. The process according to claim 1, wherein said sulfonamide trifluoroalkyl substituted alcohol is of the structure:

3. The process according to claim 1, wherein said sulfonyl chloride is of the structure:

4. The process according to claim 3, wherein R5 is chlorine.

5. The process according to claim 1, wherein said sulfonamide trifluoroalkyl substituted alcohol is of the structure:

6. The process according to claim 1, wherein said sulfonyl chloride is of the structure:

7. The process according to claim 6, wherein said sulfonyl chloride is of the structure:

8. The process according to claim 1, wherein said trifluoroalkyl substituted amino alcohol is of the structure:

9. The process according to claim 1, wherein said trifluoroalkyl substituted amino alcohol is of the structure:

10. The process according to claim 1, wherein R4 is CH(CH3)CF3.

11. The process according to claim 1, wherein said trifluoroalkyl substituted amino alcohol is (2S)-2-amino-4,4,4-trifluoro-3-(trifluoromethyl)butan-1-ol.

12. The process according to claim 11, wherein said sulfonamide trifluoroalkyl substituted alcohol is 5-Chloro-[N-[(1S)-3,3,3-trifluoro-1-(hydroxymethyl)-2-(trifluoromethyl)propyl]thiophene-2-sulfonamide.

13. The process according to claim 11, wherein said sulfonamide trifluoroalkyl substituted alcohol is 4-Chloro-[N-[(1S)-3,3,3-trifluoro-1-(hydroxymethyl)-2-(trifluoromethyl)propyl]benzenesulfonamide.

14. The process according to claim 1, wherein said base/solvent system is isopropyl acetate and 4-methylmorpholine.

15. The process according to claim 1, wherein said base/solvent system is tetrahydrofuran and Hünig's base.

16. The process according to claim 1, wherein said base/solvent system is acetonitrile and 4-methyl morpholine.

17. The process according to claim 1, wherein said base/solvent system is propionitrile and 4-methyl morpholine.

18. The process according to claim 1, wherein said base/solvent system is toluene and 4-methyl morpholine.

19. The process according to claim 1, further comprising isolating said sulfonamide trifluoroalkyl substituted alcohol by performing a solvent exchange with heptane.

20. A process for preparing 5-chloro-[N-(1S)-3,3,3-trifluoro-1-(hydroxymethyl)-2-(trifluoromethyl)propyl]thiophene-2-sulfonamide, comprising reacting (2S)-2-amino-4,4,4-trifluoro-3-(trifluoromethyl)butan-1-ol, 5-chlorothiophene-2-sulfonyl chloride, and 4-methylmorpholine in isopropyl acetate.

21. The process according to claim 20, further comprising isolating said 5-chloro-[N-(1S)-3,3,3-trifluoro-1-(hydroxymethyl)-2-(trifluoromethyl)propyl]thiophene-2-sulfonamide by exchanging said isopropyl acetate with heptane.

22. A process for preparing 4-chloro-[N-(1S)-3,3,3-trifluoro-1-(hydroxymethyl)-2-(trifluoromethyl)propyl]benzenesulfonamide, comprising reacting (2S)-2-amino-4,4,4-trifluoro-3-(trifluoromethyl)butan-1-ol, 4-chlorobenzene-2-sulfonyl chloride, and 4-methylmorpholine in isopropyl acetate.

23. The process according to claim 22, further comprising isolating said 4-chloro-[N-(1S)-3,3,3-trifluoro-1-(hydroxymethyl)-2-(trifluoromethyl)propyl]benzenesulfonamide by exchanging said isopropyl acetate with heptane.