Cesium carbonate → 4-(Trifluoromethyl)-2-(6-(trifluoromethyl)pyridin-3-yloxy)benzonitrile

HRID 538834Notes

Reaction equation

HRID 538834 reaction equation
F[C:2]1[CH:9]=[C:8]([C:10]([F:13])([F:12])[F:11])[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].[F:14][C:15]([F:24])([F:23])[C:16]1[N:21]=[CH:20][C:19]([OH:22])=[CH:18][CH:17]=1.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C.O>[F:11][C:10]([F:13])([F:12])[C:8]1[CH:7]=[CH:6][C:3]([C:4]#[N:5])=[C:2]([O:22][C:19]2[CH:20]=[N:21][C:16]([C:15]([F:24])([F:14])[F:23])=[CH:17][CH:18]=2)[CH:9]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 5189732-Fluoro-4-(trifluoromethyl)benzonitrileHCID 27833885-Hydroxy-2-(trifluoromethyl)pyridine

Product 1

HCID 576877094-(Trifluoromethyl)-2-(6-(trifluoromethyl)pyridin-3-yloxy)benzonitrileYield 87.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 2-fluoro-4-(trifluoromethyl)benzonitrile (0.19 g, 1.0 mmol), 6-(trifluoromethyl)pyridin-3-ol (0.16 g, 1.0 mmol), and Cs2CO3 (0.33 g, 1 mmol) in DMF (10 mL) was stirred at 60° C. for 18 hours. The reaction was diluted with water and extracted with ethyl acetate. The combined extracts were washed with brine and water, dried over sodium sulfate, and evaporated. The residue was purified by column chromatography on silica gel with 0-15% ethyl acetate in hexanes to give 4-(trifluoromethyl)-2-(6-(trifluoromethyl)pyridin-3-yloxy)benzonitrile (0.29 g, 87% yield). LC/MS: m/z 333.5 (M+H)+ at 1.83 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)).

Workup

  1. extractionextracted with ethyl acetate
  2. washThe combined extracts were washed with brine and water
  3. dry with materialdried over sodium sulfate
  4. customevaporated
  5. customThe residue was purified by column chromatography on silica gel with 0-15% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-bee6dae99c094600bd10d5a929fc1377
Source dataset
uspto-grants-2014_10
Patent number
US08865771B2

Reaction notes

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