Hydrochloric Acid → HCID 10667925, compound

HRID 865032Notes

Reaction equation

HRID 865032 reaction equation
[F:1][C:2]([F:10])([F:9])[C:3]([OH:8])([CH3:7])[C:4](O)=[O:5].S(Cl)(Cl)=O.[CH3:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[S:22]([C:25]1[CH:30]=[CH:29][C:28]([NH2:31])=[CH:27][CH:26]=1)(=[O:24])=[O:23].Cl>CN(C)C(=O)C>[CH3:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[S:22]([C:25]1[CH:26]=[CH:27][C:28]([NH:31][C:4](=[O:5])[C:3]([OH:8])([CH3:7])[C:2]([F:10])([F:9])[F:1])=[CH:29][CH:30]=1)(=[O:24])=[O:23]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 24386Thionyl ChlorideHCID 460655HCID 460655, compoundHCID 27751253,3,3-Trifluoro-2-hydroxy-2-methylpropanoic acid

Product 1

HCID 10667925HCID 10667925, compoundYield 77%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

To a stirred, cooled (-15° C.) solution of 3,3,3-trifluoro-2-hydroxy-2-methyl propanoic acid (1.42 g, 9.0 mmol) in N,N-dimethylacetamide (13 mL) was rapidly added thionyl chloride (1.13 g, 9.5 mmol) and the mixture (a precipitate formed after a few minutes) stirred at -20° C. to -10° C. for 1 hour. 4-(2-Methylphenylsulfonyl)benzenamine (1.48 g, 6.0 mmol) was then added in one portion, washed in with 2 mL of N,N-dimethylacetamide and the mixture allowed to stir at room temperature overnight. The solution was poured into water, the cloudy solution decanted from the resulting gum and filtered through a thin pad of Celite. The Celite pad was washed with methylene chloride and the solution added to a solution of the gum in methylene chloride. The combined methylene chloride solution was dried (MgSO4), filtered and the solvent removed in vacuo. The resulting gum was dissolved in a few mL of methanol and added dropwise to 100 mL of rapidly stirred 3N HCl. The aqueous phase was decanted from the gum, the gum dissolved in methylene chloride, dried (MgSO4), filtered and the solvent removed in vacuo. The residue was dissolved in 125 mL of methylene chloride and heated on a steam bath as 100 mL of hexane was slowly added to replace the methylene chloride. When a volume of 125 mL was reached more hexane (ca. 50 mL) was added to the cloud point. After cooling overnight the resulting solid was filtered to yield impure product. This material was further stirred with 300 mL of 0.5N HCl for 45 min., the aqueous phase decanted off and the residual gum dissolved in methylene chloride, dried (MgSO4), filtered and the solvent removed in vacuo. The material was dissolved in 100 mL of methylene chloride, 50 mL of hexane added and the solution heated on a steam bath to a final volume of 100 mL. After cooling the resulting solid was filtered and dried at 100°-120° C./0.1 tort. for 2.5 hours to yield the title propanamide (1.78 g, 77%) as a light tan solid; mp 126°-128° C. 1H-NMR (300 MHz, d6 -DMSO): 1.58 (s, 3H, CH3), 2.39 (s, 3H, aryl CH3), 7.37-8.10 (m, 8H, aromatic), 7.6 (broad s, 1H, OH), 10.4 (broad s, 1H, NH). MS (CI, CH4): 388(M+1).

Workup

  1. customthe mixture (a precipitate formed after a few minutes)
  2. washwashed in with 2 mL of N,N-dimethylacetamide
  3. stirringto stir at room temperature overnight
  4. additionThe solution was poured into water
  5. customthe cloudy solution decanted from the resulting gum
  6. filtrationfiltered through a thin pad of Celite
  7. washThe Celite pad was washed with methylene chloride
  8. additionthe solution added to a solution of the gum in methylene chloride
  9. dry with materialThe combined methylene chloride solution was dried (MgSO4)
  10. filtrationfiltered
  11. customthe solvent removed in vacuo
  12. dissolutionThe resulting gum was dissolved in a few mL of methanol
  13. additionadded dropwise to 100 mL of rapidly stirred 3N HCl
  14. customThe aqueous phase was decanted from the gum
  15. dissolutionthe gum dissolved in methylene chloride
  16. dry with materialdried (MgSO4)
  17. filtrationfiltered
  18. customthe solvent removed in vacuo
  19. dissolutionThe residue was dissolved in 125 mL of methylene chloride
  20. temperatureheated on a steam bath as 100 mL of hexane
  21. additionwas slowly added
  22. additionwas added to the cloud point
  23. temperatureAfter cooling overnight the resulting solid
  24. filtrationwas filtered
  25. customto yield impure product
  26. customthe aqueous phase decanted off
  27. dissolutionthe residual gum dissolved in methylene chloride
  28. dry with materialdried (MgSO4)
  29. filtrationfiltered
  30. customthe solvent removed in vacuo
  31. dissolutionThe material was dissolved in 100 mL of methylene chloride
  32. addition50 mL of hexane added
  33. temperaturethe solution heated on a steam bath to a final volume of 100 mL
  34. temperatureAfter cooling the resulting solid
  35. filtrationwas filtered
  36. customdried at 100°-120° C./0.1 tort

Sources & evidence

ORD record
ord-93a58bc277064e20bfb403e9a3ce9c08
Source dataset
uspto-grants-1996_10
Patent number
US05565465

Reaction notes

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