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

HRID 2259682Notes

Reaction equation

HRID 2259682 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.[NH2:15][C:16]1[CH:30]=[CH:29][C:19]([C:20]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=2[F:28])=[O:21])=[CH:18][CH:17]=1.O>CN(C)C(=O)C>[F:28][C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=1[C:20]([C:19]1[CH:18]=[CH:17][C:16]([NH:15][C:4](=[O:5])[C:3]([OH:8])([CH3:7])[C:2]([F:10])([F:9])[F:1])=[CH:30][CH:29]=1)=[O:21]

Participants

6

Reactant 4

HCID 962WaterHCID 24386Thionyl ChlorideHCID 27751253,3,3-Trifluoro-2-hydroxy-2-methylpropanoic acidHCID 105128532-Fluoro-4'-aminobenzophenone

Product 1

HCID 10546096N-[4-(2-Fluorophenylcarbonyl)phenyl]-3,3,3-trifluoro-2-hydroxy-2-methylpropanamideYield 75.3%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

To a stirred, cooled (-20° C.) solution of 3,3,3-trifluoro-2-hydroxy-2-methylpropanoic acid (1.10 g, 7.0 mmol) in N,N-dimethylacetamide (10 mL) was added thionyl chloride (0.83 g, 7.0 mmol) and the mixture stirred at -10° to -15° C. for 1 hour. 4-Amino-2'-fluoro benzophenone (1.00 g, 4.6 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 to yield a brown solid. Purification by flash column chromatography (5% v/v ethyl acetate/methylene chloride) yielded the title propanamide as a white solid (1.23 g, 75%); mp 141°-142° C. 1H-NMR (300 MHz, d6-DMSO): 1.60 (s, 3H, CH3) 7.35-7.42 (m, 2H, aromatic) 7.53-7.59 (m, 2H, aromatic +OH) 7.65-7.68 (m, 1H, aromatic) 7.75 (d, 2H, J=8.5 Hz, aromatic) 7,96 (dd, 2H, J=8.6, 1.7 Hz, aromatic) 10.37 (s, 1H, NH). MS (CI, CH4): 356 (M+1). Analysis for C17H13F4NO3 : Calculated: C, 57.47; H, 3.69; N, 3.94. Found: C, 57.44; H, 3.77; N, 3.91.

Workup

  1. stirringthe reaction mixture stirred at room temperature overnight
  2. filtrationthe aqueous solution filtered
  3. customto yield a brown solid
  4. customPurification by flash column chromatography (5% v/v ethyl acetate/methylene chloride)

Sources & evidence

ORD record
ord-743276326dda4edaa970d0fd56d1f22d
Source dataset
uspto-grants-1995_12
Patent number
US05474999

Reaction notes

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