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

HRID 1769770Notes

Reaction equation

HRID 1769770 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).

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-2fc3a27dd79f4bb395670bfa183e57f6
Source dataset
uspto-grants-1995_01
Patent number
US05382598

Reaction notes

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