Water → HCID 10785546, compound

HRID 2259691Notes

Reaction equation

HRID 2259691 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 3N 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, d 6-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). Analysis for C17H12F5NO3.0.25 H2O: Calculated: C, 54.05; H, 3.33; N, 3.70. Found: C, 54.01; H, 3.17; N, 3.68.

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 and 3N HCl (1×50 mL)
  4. dry with materialdried (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-c9cda56f98d546c7827249c986b2b9c8
Source dataset
uspto-grants-1995_12
Patent number
US05474999

Reaction notes

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