Water → N-[4-(4-Pyridinylsulfonyl)phenyl]-2-hydroxy-2-methyl-3,3,3-trifluoropropanamide

HRID 2259662Notes

Reaction equation

HRID 2259662 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][C:18]([S:21]([C:24]2[CH:29]=[CH:28][C:27]([NH2:30])=[CH:26][CH:25]=2)(=[O:23])=[O:22])=[CH:17][CH:16]=1.O>CN(C)C(=O)C>[N:15]1[CH:16]=[CH:17][C:18]([S:21]([C:24]2[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]=2)(=[O:23])=[O:22])=[CH:19][CH:20]=1

Participants

6

Reactant 4

HCID 962WaterHCID 24386Thionyl ChlorideHCID 4595324-SulfanilylpyridineHCID 27751253,3,3-Trifluoro-2-hydroxy-2-methylpropanoic acid

Product 1

HCID 9864353N-[4-(4-Pyridinylsulfonyl)phenyl]-2-hydroxy-2-methyl-3,3,3-trifluoropropanamideYield 60.4%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

To a stirred, cooled (-20° C.) solution of 3,3,3-trifluoro-2-hydroxy-2-methylpropanoic acid (4.28 g, 30.5 mmol) in N,N-dimethylacetamide (30 mL) was added thionyl chloride (3.63 g, 30.5 mmol) and the mixture stirred at -10° to -15° C. for one hour. 4-(4-Pyridylsulfonyl)benzenamine (4.77 g, 20.4 mmol) was added in one portion and the mixture stirred at room temperature overnight. The solution was poured into water, the yellow solid filtered and purified by flash chromatography (50% v/v ethyl acetate in methylene chloride). Evaporation of the eluent and trituration of the resulting solid with hot methylene chloride yielded the title propanamide (4.61 g, 60%) as an off-white solid; mp 255°-257° C. 1H-NMR (300 MHz, d6 -DMSO): 1.71 (s, 3H, CH3), 7.71 (s, 1H, OH), 8.01 (d, 2H, J=4.5 Hz, aromatic), 8.12 (d, 2H, J=7.1 Hz, aromatic), 8.19 (d, 2H, J=7.1 Hz, aromatic), 9.00 (d, 2H, J=4.5 Hz, aromatic), 10.61 (s, 1H, NH). MS (CI, CH4): 375(M+1). Analysis for C15H13F3N2O4S: Calculated: C, 48.12; H, 3.51; N, 7.48 Found: C, 48.02; H, 3.59; N, 7.42

Workup

  1. stirringthe mixture stirred at room temperature overnight
  2. filtrationthe yellow solid filtered
  3. custompurified by flash chromatography (50% v/v ethyl acetate in methylene chloride)
  4. customEvaporation of the eluent and trituration of the resulting solid with hot methylene chloride

Sources & evidence

ORD record
ord-be8b58de29464119b5ed33f1790ac7e6
Source dataset
uspto-grants-1995_12
Patent number
US05474999

Reaction notes

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