Benzyl Alcohol → 4-Amino-3-benzyloxybenzonitrile

HRID 393670

Reaction equation

HRID 393670 reaction equation
[H-].[Na+].[CH2:3]([OH:10])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[NH2:11][C:12]1[CH:19]=[CH:18][C:15]([C:16]#[N:17])=[CH:14][C:13]=1Cl>CN1C(=O)CCC1>[NH2:11][C:12]1[CH:19]=[CH:18][C:15]([C:16]#[N:17])=[CH:14][C:13]=1[O:10][CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

Participants

5

Reactant 3

HCID 244Benzyl AlcoholHCID 24758Sodium hydrideHCID 5198964-Amino-3-chlorobenzonitrile

Product 1

HCID 226465344-Amino-3-benzyloxybenzonitrileYield 31%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
50 °C

Procedure

Sodium hydride (2.7 g, 67.5 mmol) was suspended in NMP (75 ml) and benzyl alcohol (7.3 g, 67.6 mmol) was added over 10 minutes. When the addition was complete the solution was stirred at 50° C. for 30 minutes. 4-Amino-3-chlorobenzonitrile (10.3 g, 67.5 mmol), (Synthesis 1985, 669), was added and the mixture was heated at 120-130° C. for 4 hours. After cooling to ambient temperature the mixture was partitioned between water and ether. The ether extracts were washed with brine, dried (MgSO4), the insoluble materials were removed by filtration and the volatiles were removed by evaporation. The crude product was purified by flash chromatography eluting with ether/isohexanes (1/1 increasing to 1/0). The purified product was recrystallized from ethyl acetate/isohexanes to give 4-amino-3-benzyloxybenzonitrile (4.7 g, 31%).

Workup

  1. additionWhen the addition
  2. temperaturethe mixture was heated at 120-130° C. for 4 hours
  3. temperatureAfter cooling to ambient temperature the mixture
  4. customwas partitioned between water and ether
  5. washThe ether extracts were washed with brine
  6. dry with materialdried (MgSO4)
  7. customthe insoluble materials were removed by filtration
  8. customthe volatiles were removed by evaporation
  9. customThe crude product was purified by flash chromatography
  10. washeluting with ether/isohexanes (1/1 increasing to 1/0)
  11. customThe purified product was recrystallized from ethyl acetate/isohexanes

Sources & evidence

ORD record
ord-9b59084e48664d918ebd4ef7214d55e2
Source dataset
uspto-grants-2004_10
Patent number
US06809097B1

Linked notes

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