Water → N-[3-Fluoro-4-(phenylsulfonyl)phenyl]-3,3,3-trifluoro-2-hydroxy-2methylpropanamide

HRID 327197Notes

Reaction equation

HRID 327197 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.[F:15][C:16]1[CH:17]=[C:18]([NH2:31])[CH:19]=[CH:20][C:21]=1[S:22]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)(=[O:24])=[O:23].O>CN(C)C(=O)C>[F:15][C:16]1[CH:17]=[C:18]([NH:31][C:4](=[O:5])[C:3]([OH:8])([CH3:7])[C:2]([F:10])([F:9])[F:1])[CH:19]=[CH:20][C:21]=1[S:22]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)(=[O:24])=[O:23]

Participants

6

Reactant 4

HCID 962WaterHCID 24386Thionyl ChlorideHCID 27751253,3,3-Trifluoro-2-hydroxy-2-methylpropanoic acidHCID 107532343-Fluoro-4-(phenyl sulfonyl)benzeneamine

Product 1

HCID 10834289N-[3-Fluoro-4-(phenylsulfonyl)phenyl]-3,3,3-trifluoro-2-hydroxy-2methylpropanamideYield 68%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

To a stirred, cooled (-20° C.) solution of 3,3,3-trifluoro2-hydroxy-2-methylpropanoic acid (0.71 g, 4.5 mmol) in N,N-dimethylacetamide (10 mL) was added thionyl chloride (0.54 g, 4.5 mmol) and the mixture stirred at -10° to -15° C. for 1 hour. 3-Fluoro-4-(phenyl sulfonyl)benzeneamine (0.75 g, 3.0 mmol) was added in one portion and the reaction mixture stirred at room temperature overnight. The mixture was poured into water and the aqueous solution filtered through Celite. The Celite was washed with methylene chloride (75 mL), the organic extract dried (MgSO4) and concentrated in vacuo to a tan solid. Purification by flash column chromatography (5% v/v ethyl acetate/methylene chloride) yielded the title propanamide as a white solid (0.79 g, 68%); mp 147°-149° C. 1H--NMR (250 MHz, d6--DMSO): 1.58 (s, 3H, CH3) 7.65-7.69 (m, 4 H, aromatic+OH) 7.74 (d, 1H, J=7.2 Hz, aromatic) 7.83-7.94 (m, 3H, aromatic) 8.02 (t, 1H, J=8.3 Hz, aromatic) 10.61 (s, 1H, NH). MS (CI, CH4): 392 (M+1).

Workup

  1. stirringthe reaction mixture stirred at room temperature overnight
  2. filtrationthe aqueous solution filtered through Celite
  3. washThe Celite was washed with methylene chloride (75 mL)
  4. extractionthe organic extract
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated in vacuo to a tan solid
  7. customPurification by flash column chromatography (5% v/v ethyl acetate/methylene chloride)

Sources & evidence

ORD record
ord-b62f8f0dc0d147d0a378cc309736695c
Source dataset
uspto-grants-1993_12
Patent number
US05272163

Reaction notes

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