Hydroxylamine HCl → 4-(Benzyloxy)-3-hydroxybenzonitrile

HRID 1713294Notes

Reaction equation

HRID 1713294 reaction equation
[CH2:1]([O:8][C:9]1[CH:16]=[CH:15][C:12]([CH:13]=O)=[CH:11][C:10]=1[OH:17])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl-].O[NH3+:20].C([O-])(=O)C.[Na+]>O.C(O)C>[CH2:1]([O:8][C:9]1[CH:16]=[CH:15][C:12]([C:13]#[N:20])=[CH:11][C:10]=1[OH:17])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 21645Hydroxylamine HClHCID 517045Sodium AcetateHCID 5613694-Benzyloxy-3-hydroxybenzaldehyde

Product 1

HCID 154534514-(Benzyloxy)-3-hydroxybenzonitrileYield 5.3%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent2×

Conditions

Temperature
80 °C

Procedure

A mixture of 4-benzyloxy-3-hydroxybenzaldehyde (19.0 g), hydroxylammonium chloride (8.6 g), sodium acetate (13.7 g), water (30 mL) and ethanol (150 mL) was stirred at 80° C. for 8 hours. Water (100 mL) was added to the reaction mixture and the whole was extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was dissolved in dichloromethane (100 mL), and then pyridine (20 mL) was added. Trifluoroacetic anhydride (35.3 mL) was added dropwise under ice-cooling, and the resulting mixture was stirred at room temperature for 6 hours. Two mol/L hydrochloric acid was added to the reaction mixture and the whole was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium hydrogen carbonate and brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (eluent: ethyl acetate/hexane=1/10) to give the title compound (1.0 g).

Workup

  1. extractionthe whole was extracted with ethyl acetate
  2. washThe organic layer was washed with brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. dissolutionThe residue was dissolved in dichloromethane (100 mL)
  6. additionpyridine (20 mL) was added
  7. additionTrifluoroacetic anhydride (35.3 mL) was added dropwise under ice-
  8. temperaturecooling
  9. stirringthe resulting mixture was stirred at room temperature for 6 hours
  10. additionTwo mol/L hydrochloric acid was added to the reaction mixture
  11. extractionthe whole was extracted with ethyl acetate
  12. washThe organic layer was washed with saturated aqueous sodium hydrogen carbonate and brine
  13. dry with materialdried over anhydrous magnesium sulfate
  14. concentrationconcentrated under reduced pressure
  15. customThe residue was purified by column chromatography on silica gel (eluent: ethyl acetate/hexane=1/10)

Sources & evidence

ORD record
ord-d162ba731465461c8ad5fff80b69bac2
Source dataset
uspto-grants-2010_09
Patent number
US07795236B2

Reaction notes

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