Sodium hydride → 2-(alpha-Cyano-4-fluorobenzyl)-5-methylpyridine

HRID 856634Notes

Reaction equation

HRID 856634 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]#[N:10])=[CH:4][CH:3]=1.Br[C:12]1[CH:17]=[CH:16][C:15]([CH3:18])=[CH:14][N:13]=1.CC1C=CC(S([O-])=O)=CC=1.[Na+].[H-].[Na+]>C1COCC1.O>[C:9]([CH:8]([C:12]1[CH:17]=[CH:16][C:15]([CH3:18])=[CH:14][N:13]=1)[C:5]1[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=1)#[N:10]

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 68016Benzeneacetonitrile, 4-fluoro-HCID 5642162-Bromo-5-methylpyridineHCID 2723791Sodium p-toluenesulfinate

Product 1

HCID 114134832-(alpha-Cyano-4-fluorobenzyl)-5-methylpyridineYield 66.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Under argon atmosphere, to a mixture of 4-fluorophenylacetonitrile (3.97 g), 2-bromo-5-methylpyridine (5.00 g) and sodium 4-methylphenylsulfinate (10.48 g) in THF (125 ml) was added sodium hydride (2.35 g, 60%) at 0° C. and the mixture was heated to reflux for 6 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 2-(α-cyano-4-fluorobenzyl)-5-methylpyridine (4.35 g) as yellow oil.

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux for 6 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-206ec365cf874c788894c440c4d0cf99
Source dataset
uspto-grants-2007_08
Patent number
US07262185B2

Reaction notes

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