Water → N-[4-(2-Pyrimidinylsulfonyl)phenyl]-3,3,3-trifluoro-2-hydroxy-2-methyl propanamide

HRID 2259663Notes

Reaction equation

HRID 2259663 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.[N:15]1[CH:20]=[CH:19][CH:18]=[N:17][C:16]=1[S:21]([C:24]1[CH:29]=[CH:28][C:27]([NH2:30])=[CH:26][CH:25]=1)(=[O:23])=[O:22].O>CN(C)C(=O)C>[N:15]1[CH:20]=[CH:19][CH:18]=[N:17][C:16]=1[S:21]([C:24]1[CH:29]=[CH:28][C:27]([NH:30][C:4](=[O:5])[C:3]([OH:8])([CH3:7])[C:2]([F:10])([F:9])[F:1])=[CH:26][CH:25]=1)(=[O:22])=[O:23]

Participants

6

Reactant 4

HCID 962WaterHCID 24386Thionyl ChlorideHCID 27751253,3,3-Trifluoro-2-hydroxy-2-methylpropanoic acidHCID 218172744-(2-Pyrimidylsulfonyl)aniline

Product 1

HCID 10667166N-[4-(2-Pyrimidinylsulfonyl)phenyl]-3,3,3-trifluoro-2-hydroxy-2-methyl propanamideYield 66.6%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

To a stirred, cooled (-20° C.) solution of 3,3,3-trifluoro-2-hydroxy-2-methylpropanoic acid (1.01 g, 6.4 mmol) in N,N-dimethylacetamide (10 mL) was added thionyl chloride (0.76 g, 6.4 mmol) and the mixture stirred at -10° to 15° C. for one hour. 4-(2-Pyrimidylsulfonyl)benzenamine (1.00 g, 4.2 mmol) was added in one portion to the orange solution and the mixture stirred at room temperature overnight. The brown mixture was poured into water and extracted with ethyl acetate (2×50 mL). The combined organic portions were washed with water, dried (MgSO4), filtered, and the solvent distilled to yield a tan solid. Flash chromatography of the solid (eluted with 10% v/v ethyl acetate in methylene chloride) and evaporation of the eluent yielded the title propanamide (1.05 g, 66%) as a white solid; mp 187°-190° C. 1H-NMR (300 MHz, d6 -DMSO): 1.60 (s, 3H, CH3), 7.59 (s, 1H, OH), 7.79 (t, 1H, J=4.9 Hz, aromatic), 7.96 (d, 2H, J=8.9 Hz, aromatic), 8.06 (d, 2H, J=8.9 Hz, aromatic), 9.02 (d, 2H, J=4.8 Hz, aromatic), 10.49 (s, 1H, NH). MS (CI, CH4): 376 (M+1). Analysis for C14H12F3N3O4S: Calculated: C, 44.80; H, 3.22; N, 11.20 Found: C, 44.86; H, 3.36; N, 11.06

Workup

  1. stirringthe mixture stirred at room temperature overnight
  2. extractionextracted with ethyl acetate (2×50 mL)
  3. washThe combined organic portions were washed with water
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. distillationthe solvent distilled
  7. customto yield a tan solid
  8. washFlash chromatography of the solid (eluted with 10% v/v ethyl acetate in methylene chloride) and
  9. customevaporation of the eluent

Sources & evidence

ORD record
ord-69449fe520de409cab44a668e40a1ccf
Source dataset
uspto-grants-1995_12
Patent number
US05474999

Reaction notes

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