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

HRID 327164Notes

Reaction equation

HRID 327164 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-dimethyl-acetamide (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).

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-cd0f0573488e4df4b62312b9a84128dd
Source dataset
uspto-grants-1993_12
Patent number
US05272163

Reaction notes

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