Sodium hydride → 2-(alpha-Cyano-4-fluorobenzyl)-3-methylpyridine

HRID 856632Notes

Reaction equation

HRID 856632 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[C:17]([CH3:18])=[CH:16][CH:15]=[CH:14][N:13]=1.CC1C=CC(S([O-])=O)=CC=1.[Na+].[H-].[Na+]>C1COCC1.O>[C:9]([CH:8]([C:12]1[C:17]([CH3:18])=[CH:16][CH:15]=[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 2208322-Bromo-3-methylpyridineHCID 2723791Sodium p-toluenesulfinate

Product 1

HCID 112068942-(alpha-Cyano-4-fluorobenzyl)-3-methylpyridineYield 78.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Under argon atmosphere, to a mixture of 4-fluorophenylacetonitrile (3.97 g), 2-bromo-3-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. to the mixture, and the mixture was heated to reflux for 3.5 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 1:3), to give 2-(α-cyano-4-fluorobenzyl)-3-methylpyridine (5.14 g) as brown oil.

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux for 3.5 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 1:3)

Sources & evidence

ORD record
ord-a0cecc95e7184afdb2dd50d5b4c1bce9
Source dataset
uspto-grants-2007_08
Patent number
US07262185B2

Reaction notes

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