Potassium Carbonate → 3-{1-ethyl-5-[4-(trifluoromethyl)phenoxy]-1H-pyrazol-3-yl}benzonitrile

HRID 540747Notes

Reaction equation

HRID 540747 reaction equation
F[C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][CH:3]=1.[CH2:12]([N:14]1[C:18](=[O:19])[CH:17]=[C:16]([C:20]2[CH:21]=[C:22]([CH:25]=[CH:26][CH:27]=2)[C:23]#[N:24])[NH:15]1)[CH3:13].C(=O)([O-])[O-].[K+].[K+]>CS(C)=O>[CH2:12]([N:14]1[C:18]([O:19][C:2]2[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][CH:3]=2)=[CH:17][C:16]([C:20]2[CH:21]=[C:22]([CH:25]=[CH:26][CH:27]=2)[C:23]#[N:24])=[N:15]1)[CH3:13]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 67873Benzene, 1-fluoro-4-(trifluoromethyl)-HCID 671110593-(1-ethyl-5-oxo-2,5-dihydro-1H-pyrazol-3-yl)benzonitrile

Product 1

HCID 671116173-{1-ethyl-5-[4-(trifluoromethyl)phenoxy]-1H-pyrazol-3-yl}benzonitrileYield 44%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
160 °C

Procedure

1-fluoro-4-(trifluoromethyl)benzene (22.9 mL, 180 mmol, 6.00 equiv) was added to a mixture of 3-(1-ethyl-5-oxo-2,5-dihydro-1H-pyrazol-3-yl)benzonitrile (6.40 g, 30.0 mmol, 1 equiv) and potassium carbonate (12.4 g, 90.0 mmol, 3.00 equiv) in dimethyl sulfoxide (60 mL) in a high pressure reaction vessel. The vessel was sealed, and the reaction mixture was heated to 160° C. After stirring for 16 hours, the high pressure vessel was cooled to 22° C. and the reaction mixture was partitioned between ethyl acetate and water. The organic layer was washed with saturated aqueous sodium chloride solution, and the washed solution was dried over sodium sulfate. The dried solution was filtered, and the filtrate was concentrated. The residue was purified by flash-column chromatography (hexanes, grading to 50% ethyl acetate-hexanes) to afford 3-{1-ethyl-5-[4-(trifluoromethyl)phenoxy]-1H-pyrazol-3-yl}benzonitrile (4.70 g, 44%) as a white solid. Calcd (M+1)+: 357.1. Found: 358.0.

Workup

  1. customThe vessel was sealed
  2. temperaturethe high pressure vessel was cooled to 22° C.
  3. customthe reaction mixture was partitioned between ethyl acetate and water
  4. washThe organic layer was washed with saturated aqueous sodium chloride solution
  5. dry with materialthe washed solution was dried over sodium sulfate
  6. filtrationThe dried solution was filtered
  7. concentrationthe filtrate was concentrated
  8. customThe residue was purified by flash-column chromatography (hexanes, grading to 50% ethyl acetate-hexanes)

Sources & evidence

ORD record
ord-5df46cb898d2401c8dcd447ed9f0006b
Source dataset
uspto-grants-2014_10
Patent number
US08871796B2

Reaction notes

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