Isoamyl Nitrite → 2-Ethoxy-4-(trifluoromethyl)benzonitrile

HRID 1990811Notes

Reaction equation

HRID 1990811 reaction equation
N[C:2]1[CH:9]=[C:8]([C:10]([F:13])([F:12])[F:11])[C:7](OCC)=[CH:6][C:3]=1[C:4]#[N:5].N([O:19][CH2:20][CH2:21]C(C)C)=O>C1COCC1.C([O-])(O)=O.[Na+]>[CH2:20]([O:19][C:2]1[CH:9]=[C:8]([C:10]([F:11])([F:12])[F:13])[CH:7]=[CH:6][C:3]=1[C:4]#[N:5])[CH3:21]

Participants

5

Reactant 2

HCID 8053Isoamyl NitriteHCID 66650419HCID 66650419, compound

Product 1

HCID 450943912-Ethoxy-4-(trifluoromethyl)benzonitrileYield 85%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a solution of 2-amino-5-ethoxy-4-trifluoromethyl-benzonitrile (31.62 g, 137.4 mmol, 1.0 equiv) in anhydrous THF (410 mL) was added isoamyl nitrite (40.4 mL, 302 mmol, 2.2 equiv) and the mixture was heated to reflux for 16 h. The solvent was removed by evaporation under reduced pressure to give an orange oil which was dissolved in a sat. solution of NaHCO3 and extracted three times with diethyl ether. The combined organic phases were washed with 1 N HCl and a sat. solution of sodium chloride and the organic phases dried over Na2SO4. Removal of the solvent by evaporation under reduced pressure left an orange oil which was purified by double Kugelrohr distillation (up to 160° C. bath temperature at 1.5 mbar) yielding 25.1 g (85%) of the title compound as a light yellow solid upon solidification. MS (EI): 185.1 [M]+.

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux for 16 h
  3. customThe solvent was removed by evaporation under reduced pressure
  4. customto give an orange oil which
  5. extractionextracted three times with diethyl ether
  6. washThe combined organic phases were washed with 1 N HCl
  7. dry with materiala sat. solution of sodium chloride and the organic phases dried over Na2SO4
  8. customRemoval of the solvent
  9. customby evaporation under reduced pressure
  10. waitleft an orange oil which
  11. distillationwas purified by double Kugelrohr distillation (up to 160° C. bath temperature at 1.5 mbar)

Sources & evidence

ORD record
ord-ed341707e4e84a259c561f8cc22ca62d
Source dataset
uspto-grants-2010_01
Patent number
US07645753B2

Reaction notes

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