2-Chloro-6-methylbenzonitrile → 2-Fluoro-6-methylbenzonitrile

HRID 1634122Notes

Reaction equation

HRID 1634122 reaction equation
Cl[C:2]1[CH:9]=[CH:8][CH:7]=[C:6]([CH3:10])[C:3]=1[C:4]#[N:5].[F-:11].[Cs+]>CS(C)=O.O>[F:11][C:2]1[CH:9]=[CH:8][CH:7]=[C:6]([CH3:10])[C:3]=1[C:4]#[N:5]

Participants

5

Reactant 2

HCID 230532-Chloro-6-methylbenzonitrileHCID 25953Cesium fluoride

Product 1

HCID 186771512-Fluoro-6-methylbenzonitrileYield 66%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of 2-chloro-6-methylbenzonitrile (5 g, 33.0 mmol) and CsF (14 g, 92.2 mmol) in DMSO (30 ml) was heated at 140° C. for 15 hr and then allowed to cool to room temperature. It was diluted with water, extracted with dichloromethane, washed with brine, dried (Na2SO4) and concentrated to give 2-fluoro-6-methylbenzonitrile (2.93 g, 66%). A mixture of the above nitrile (250 mg), 1-(4-aminophenyl)-3-(3-pyridyl)-5-ethylpyrazole (200 mg, 0.76 mmol) and Raney Ni (50% in water, 100 mg) in glacial acetic acid (15 ml) was shaken in a Parr apparatus under H2 (40 psi) for 7 hr. The catalyst was removed by filtration and the solvent was evaporated. Chromatography on silica gel (hexane/ethyl acetate=2:1) afforded the title compound (146 mg). 1H-NMR (CDCl3): 1.30 (t, J=7.5 Hz, 3H), 2.46 (s, 3H), 2.67 (q, J=7.5 Hz, 2H), 3.92 (bs, 1H), 4.38 (s, 2H), 6.58 (s, 1H), 6.78 (d, J=8.6 Hz, 2H), 6.99 (t, J=6.8Hz, 1H), 7.05 (d, J=7.8 Hz, 1H), 7.19-7.38 (m, 4 H), 8.20 (d, J=7.8 Hz, 1H), 8.56 (d, J=3.7Hz, 1H), 9.10 (s, 1H).

Workup

  1. temperatureto cool to room temperature
  2. extractionextracted with dichloromethane
  3. washwashed with brine
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-c3fa6bb5b6ad4723a354f854b6c8d236
Source dataset
uspto-grants-2003_01
Patent number
US06506747B1

Reaction notes

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