Acetonitrile → 3-Oxo-4-phenylbutanenitrile

HRID 1521751Notes

Reaction equation

HRID 1521751 reaction equation
[H-].[Na+].[C:3]1([CH2:9][C:10]([O:12]C)=O)[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[C:14](#[N:16])[CH3:15]>C1COCC1>[O:12]=[C:10]([CH2:9][C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1)[CH2:15][C:14]#[N:16]

Participants

5

Reactant 3

HCID 6342AcetonitrileHCID 7559Methyl phenylacetateHCID 24758Sodium hydride

Product 1

HCID 5626663-Oxo-4-phenylbutanenitrileYield 26.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a suspension of 60% sodium hydride in mineral oil (1.00 g, 25.0 mmol) in THF (40 mL) at reflux is added a solution of methyl phenylacetate (2.50 g, 16.6 mmol) and anhydrous acetonitrile (1.74 mL, 33.3 mmol) in THF (40 mL), dropwise. The mixture is stirred at reflux for 6 h, then cooled to room temperature and stirred an additional 16 h. The reaction is quenched with H2O and is stirred for 10 min, after which the mixture is diluted with ethyl acetate and saturated aqueous NaHCO3 solution. The layers are separated and the aqueous layer is extracted with ethyl acetate. The organic layers are washed with brine and dried (Na2SO4). The solvent is removed in vacuo and the crude material is purified via flash column chromatography using a gradient elution of 0-40% ethyl acetate/heptane to afford the title compound as a yellow oil (690 mg, 26%). LCMS: 160.20 (M+H+).

Workup

  1. temperatureat reflux
  2. temperatureat reflux for 6 h
  3. stirringstirred an additional 16 h
  4. customThe reaction is quenched with H2O
  5. stirringis stirred for 10 min
  6. additionafter which the mixture is diluted with ethyl acetate and saturated aqueous NaHCO3 solution
  7. customThe layers are separated
  8. extractionthe aqueous layer is extracted with ethyl acetate
  9. washThe organic layers are washed with brine
  10. dry with materialdried (Na2SO4)
  11. customThe solvent is removed in vacuo
  12. customthe crude material is purified via flash column chromatography
  13. washa gradient elution of 0-40% ethyl acetate/heptane

Sources & evidence

ORD record
ord-84239ff04092425bb36664b4cf012955
Source dataset
uspto-grants-2015_07
Patent number
US09073926B2

Reaction notes

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