Water → 4-Cyano-2-fluoropyridine

HRID 1467412Notes

Reaction equation

HRID 1467412 reaction equation
[F-:1].[Cs+].Cl[C:4]1[CH:5]=[C:6]([CH:9]=[CH:10][N:11]=1)[C:7]#[N:8].O>S1(CCCC1)(=O)=O>[F:1][C:4]1[CH:5]=[C:6]([CH:9]=[CH:10][N:11]=1)[C:7]#[N:8]

Participants

5

Reactant 3

HCID 962WaterHCID 25953Cesium fluorideHCID 5686382-Chloro-4-cyanopyridine

Product 1

HCID 120025874-Cyano-2-fluoropyridineYield 89,345.703%

Reagents, catalysts & solvents 1

HCID 31347SulfolaneSolvent

Conditions

Temperature
100 °C

Procedure

Cesium fluoride (30 g, 0.22 mmol) was slurried in 150 mL dry sulfolane and concentrated via vacuum distillation at 0.5 mm Hg. After removal of 20% of the solvent, the suspension was cooled and 2-chloroisonicotinonitrile (15 g, 0.11 mmol) was added then stirred and heated at 100° C. for 20 h. It was cooled to 25° C., poured into 200 mL water and extracted with Et2O. The ether phase was washed with water, then brine, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by column chromatography over silica gel with CH2Cl2 to give 12.0 g of 2-fluoroisonicotinonitrile as a low-melting colorless solid. MS m/z 122. 1H NMR (CDCl3): δ 8.45 (dd, 1H), 7.47 (dd, 1H), 7.24 (m, 1H).

Workup

  1. concentrationconcentrated via vacuum distillation at 0.5 mm Hg
  2. customAfter removal of 20% of the solvent
  3. temperaturethe suspension was cooled
  4. temperatureIt was cooled to 25° C.
  5. extractionextracted with Et2O
  6. washThe ether phase was washed with water
  7. dry with materialbrine, dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by column chromatography over silica gel with CH2Cl2

Sources & evidence

ORD record
ord-44c43c9507eb41d787082bb68477a298
Source dataset
uspto-grants-2015_04
Patent number
US09000162B2

Reaction notes

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