Water → HCID 10785546, compound

HRID 865262Notes

Reaction equation

HRID 865262 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:21]=[CH:20][C:19]([C:22](=[O:31])[C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([F:29])[C:24]=2[F:30])=[CH:18][CH:17]=1.O>CN(C)C(=O)C>[F:30][C:24]1[C:25]([F:29])=[CH:26][CH:27]=[CH:28][C:23]=1[C:22]([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:21][CH:20]=1)=[O:31]

Participants

6

Reactant 4

HCID 962WaterHCID 24386Thionyl ChlorideHCID 27751253,3,3-Trifluoro-2-hydroxy-2-methylpropanoic acidHCID 108235164'-Amino-2,3-difluorobenzophenone

Product 1

HCID 10785546HCID 10785546, compoundYield 70.4%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

To a stirred, cooled (-20° C.) solution of 3,3,3-trifluoro-2-hydroxy-2-methylpropanoic acid (1.02 g, 6.4 mmol) in N,N-dimethylacetamide (10 mL) was added thionyl chloride (0.77 g, 6.4 mmol) and the mixture stirred at -10° to -15° C. for 1 hour. 4'-Amino-2,3-difluorobenzophenone (1.00 g, 4.3 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 extracted with methylene chloride (2×50 mL). The combined organics were washed with water and. 3 N HCl (1×50 mL), dried (MgSO4) and concentrated in vacuo to yield a tan solid. The solid was purified by flash column chromatography (5% v/v ethyl acetate/methylene chloride). Recrystallization of the resulting solid from methylene chloride/hexane yielded the title propanamide as a white solid (1.13 g, 70%); mp 154°-155° C. 1H-NMR (250 MHz, d6-DMSO): 1.60 (s, 3H, CH3) 7.36-7.40 (m, 2H, aromatic) 7.57 (s, 1H, OH) 7.65-7.72 (m, 1H, aromatic) 7.89 (d, 2H, J=8.6 Hz, aromatic) 7.98 (d, 2H, J=8.6 Hz, aromatic) 10.40 (s, 1H, NH). MS (CI, CH4): 374 (M+1).

Workup

  1. stirringthe reaction mixture stirred at room temperature overnight
  2. extractionthe aqueous solution extracted with methylene chloride (2×50 mL)
  3. washThe combined organics were washed with water
  4. dry with material3 N HCl (1×50 mL), dried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. customto yield a tan solid
  7. customThe solid was purified by flash column chromatography (5% v/v ethyl acetate/methylene chloride)
  8. customRecrystallization of the resulting solid from methylene chloride/hexane

Sources & evidence

ORD record
ord-1bd57d2adc4d43deadbf3510e1ef0be1
Source dataset
uspto-grants-1996_10
Patent number
US05565477

Reaction notes

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