Phenol → Ethyl 5-amino-2-phenoxybenzoate

HRID 1786847Notes

Reaction equation

HRID 1786847 reaction equation
F[C:2]1[CH:12]=[CH:11][C:10]([N+:13]([O-])=O)=[CH:9][C:3]=1[C:4]([O:6][CH2:7][CH3:8])=[O:5].[C:16]1([OH:22])[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[NH2:13][C:10]1[CH:11]=[CH:12][C:2]([O:22][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[C:3]([CH:9]=1)[C:4]([O:6][CH2:7][CH3:8])=[O:5]

Participants

5

Reactant 3

HCID 996PhenolHCID 11430Potassium CarbonateHCID 12793176Ethyl 2-fluoro-5-nitrobenzoate

Product 1

HCID 53848249Ethyl 5-amino-2-phenoxybenzoateYield 82.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of ethyl 2-fluoro-5-nitrobenzoate (1.07 g), phenol (565 mg), potassium carbonate (1.38 g) and N,N-dimethylformamide (20 mL) was stirred at 80° C. for 4 hrs. The reaction mixture was concentrated under reduced pressure. Water was added to the residue and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (eluent, ethyl acetate:hexane=20:80→30:70). The object fraction was concentrated under reduced pressure and ethanol (20 mL) and 10% palladium on carbon (1.5 g) were added to the residue (1.54 g). The mixture was stirred overnight under a hydrogen stream. The catalyst was filtered off, and the filtrate was concentrated. The obtained residue was purified by silica gel column chromatography (eluent, ethyl acetate:hexane=20:80→50:50) and recrystallized from diisopropyl ether-hexane to give the title compound (1.07 g) as a pale-brown powder.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. additionWater was added to the residue
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe extract was washed with saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customThe solvent was evaporated under reduced pressure
  7. customthe obtained residue was purified by silica gel column chromatography (eluent, ethyl acetate:hexane=20:80→30:70)
  8. concentrationThe object fraction was concentrated under reduced pressure and ethanol (20 mL) and 10% palladium on carbon (1.5 g)
  9. additionwere added to the residue (1.54 g)
  10. stirringThe mixture was stirred overnight under a hydrogen stream
  11. filtrationThe catalyst was filtered off
  12. concentrationthe filtrate was concentrated
  13. customThe obtained residue was purified by silica gel column chromatography (eluent, ethyl acetate:hexane=20:80→50:50)
  14. customrecrystallized from diisopropyl ether-hexane

Sources & evidence

ORD record
ord-e1755d888fa243c2bda0a67feb7d57c2
Source dataset
uspto-grants-2009_03
Patent number
US07507740B2

Reaction notes

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