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

HRID 2259667Notes

Reaction equation

HRID 2259667 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:29]=[CH:28][C:19]([C:20]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=2)=[O:21])=[CH:18][CH:17]=1.O>CN(C)C(=O)C>[N:23]1[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=1[C:20]([C:19]1[CH:28]=[CH:29][C:16]([NH:15][C:4](=[O:5])[C:3]([OH:8])([CH3:7])[C:2]([F:10])([F:9])[F:1])=[CH:17][CH:18]=1)=[O:21]

Participants

6

Reactant 4

HCID 962WaterHCID 24386Thionyl ChlorideHCID 27751253,3,3-Trifluoro-2-hydroxy-2-methylpropanoic acidHCID 10726619(4-Aminophenyl)-2-pyridinylmethanone

Product 1

HCID 10735716N-[4-(2-Pyridylcarbonyl)phenyl]-3,3,3-trifluoro-2-hydroxy-2-methylpropanamideYield 63.3%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

To a stirred, cooled (-20° C.) solution of 3,3,3-trifluoro-2-hydroxy-2-methylpropanoic acid (1.20 g, 7.6 mmol) in N,N-dimethylacetamide (10 mL) was added thionyl chloride (0.90 g, 7.6 mmol) and the mixture stirred at -10° to -15° C. for 1 hour. 2-(4-Aminobenzoyl)pyridine (1.00 g, 5.0 mmol) was added in one portion and the reaction mixture stirred overnight at room temperature. The reaction mixture was poured into water and the aqueous solution extracted with ethyl acetate (2×50 mL). The combined organics were dried (MgSO4), filtered and the solvent removed in vacuo to yield a brown oil. Flash chromatography (eluted with 5% v/v ethyl acetate in methylene chloride) of the oil, evaporation of the eluent, and trituration with diethyl ether yielded the title propanamide (1.07 g, 63%) as a white solid; mp 151°-154° C. 1H-NMR (250 MHz, d6 -DMSO): 1.58 (s, 3 H, CH3), 7.58 (s, 1H, OH), 7.98 (d, 2H, J=8.9 Hz, aromatic), 8.06 (d, 2H, J=9.0 Hz, aromatic), 8.81 (m, 2H, aromatic), 8.97 (d, 1H, J=2.2 Hz, aromatic), 9.39 (s, 1H, aromatic), 10.48 (s, 1H, NH). MS (CI, CH4): 339(M+1). Analysis for C16H13F3N2O3 : Calculated: C, 56.81; H, 3.87; N, 8.28 Found: C, 56.50; H, 3.91; N, 8.21

Workup

  1. stirringthe reaction mixture stirred overnight at room temperature
  2. extractionthe aqueous solution extracted with ethyl acetate (2×50 mL)
  3. dry with materialThe combined organics were dried (MgSO4)
  4. filtrationfiltered
  5. customthe solvent removed in vacuo
  6. customto yield a brown oil
  7. washFlash chromatography (eluted with 5% v/v ethyl acetate in methylene chloride)
  8. customof the oil, evaporation of the eluent, and trituration with diethyl ether

Sources & evidence

ORD record
ord-4517b6f44c9343b7b6020cc710ade937
Source dataset
uspto-grants-1995_12
Patent number
US05474999

Reaction notes

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