Sodium hydride → 5-Chloro-α-(4-fluorophenyl)-2-pyridineacetonitrile

HRID 856636Notes

Reaction equation

HRID 856636 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]#[N:10])=[CH:4][CH:3]=1.Cl[C:12]1[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][N:13]=1.CC1C=CC(S([O-])=O)=CC=1.[Na+].[H-].[Na+]>C1COCC1.O>[Cl:18][C:15]1[CH:16]=[CH:17][C:12]([CH:8]([C:9]#[N:10])[C:5]2[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=2)=[N:13][CH:14]=1

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 276852,5-DichloropyridineHCID 68016Benzeneacetonitrile, 4-fluoro-HCID 2723791Sodium p-toluenesulfinate

Product 1

HCID 229385995-Chloro-α-(4-fluorophenyl)-2-pyridineacetonitrileYield 96.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Under argon atmosphere, to a mixture of 4-fluorophenylacetonitrile (9.13 g), 2-chloro-5-chloropyridine (10.0 g.) and sodium 4-methylphenylsulfinate (24.1 g) in THF (280 ml) was added sodium hydride (5.41 g, 60%) at 0° C., and the mixture was heated to reflux for 20 hours. The reaction mixture was added to water and extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over magnesium sulfate and concentrated under reduced pressure, and the obtained residue was separated and purified by column chromatography (ethyl acetate:hexane 1:4), to give 5-chloro-2-(α-cyano-4-fluorobenzyl)pyridine (16.14 g) as yellow oil.

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux for 20 hours
  3. extractionextracted with ethyl acetate
  4. washThe organic layer was washed with saturated brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customthe obtained residue was separated
  8. custompurified by column chromatography (ethyl acetate:hexane 1:4)

Sources & evidence

ORD record
ord-a0d05c25554142c99e28e7037d74ce71
Source dataset
uspto-grants-2007_08
Patent number
US07262185B2

Reaction notes

Loading…