Cesium carbonate → 2-(2-Methylpyridin-3-yloxy)-4-(trifluoromethyl)benzonitrile

HRID 79100Notes

Reaction equation

HRID 79100 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].[CH3:14][C:15]1[C:20]([OH:21])=[CH:19][CH:18]=[CH:17][N:16]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.O>[CH3:14][C:15]1[C:20]([O:21][C:2]2[CH:9]=[C:8]([C:10]([F:13])([F:12])[F:11])[CH:7]=[CH:6][C:3]=2[C:4]#[N:5])=[CH:19][CH:18]=[CH:17][N:16]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 707192-Methylpyridin-3-olHCID 5189732-Fluoro-4-(trifluoromethyl)benzonitrile

Product 1

HCID 589880732-(2-Methylpyridin-3-yloxy)-4-(trifluoromethyl)benzonitrileYield 94%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of 2-fluoro-4-(trifluoromethyl)benzonitrile (0.19 g, 1.0 mmol), 2-methylpyridin-3-ol (0.11 g, 1.0 mmol), and cesium carbonate (0.33 g, 1.0 mmol) in anhydrous DMF (5 mL) was heated at 50° C. for 16 h. The reaction was diluted with water and extracted with EtOAc. The combined extracts were washed with water, dried over Na2SO4, and evaporated under reduced pressure. The residue was purified by silica gel chromatography (0%-30% EtOAc-hexanes) to obtain 2-(2-methylpyridin-3-yloxy)-4-(trifluoromethyl)benzonitrile (0.26 g, 94% yield). 1H NMR (400 MHz, CDCl3) δ 8.50 (dd, J=4.7, 1.4 Hz, 1H), 7.85 (d, J=8.0 Hz, 1H), 7.44 (dd, J=8.1, 0.7 Hz, 1H), 7.35 (dd, J=8.1, 1.4 Hz, 1H), 7.28-7.25 (m, 1H), 6.87 (s, 1H), 2.50 (s, 3H) ppm.

Workup

  1. extractionextracted with EtOAc
  2. washThe combined extracts were washed with water
  3. dry with materialdried over Na2SO4
  4. customevaporated under reduced pressure
  5. customThe residue was purified by silica gel chromatography (0%-30% EtOAc-hexanes)

Sources & evidence

ORD record
ord-bcfe844ad5274be38422767fd75a52e4
Source dataset
uspto-grants-2014_09
Patent number
US08841483B2

Reaction notes

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