Benzene → 2-Methyl-4-methoxy-5-fluoroacetylaminophenol

HRID 2050758Notes

Reaction equation

HRID 2050758 reaction equation
C1C=CC=CC=1.[CH3:7][C:8]1[CH:13]=[C:12]([O:14][CH3:15])[C:11]([NH2:16])=[CH:10][C:9]=1[OH:17].[F:18][CH2:19][C:20](OC)=[O:21].C[O-].[Na+]>C(O)(=O)C.O>[CH3:7][C:8]1[CH:13]=[C:12]([O:14][CH3:15])[C:11]([NH:16][C:20](=[O:21])[CH2:19][F:18])=[CH:10][C:9]=1[OH:17]

Participants

7

Reactant 4

HCID 241BenzeneHCID 9959Methyl fluoroacetateHCID 10197787Phenol, 5-amino-4-methoxy-2-methyl-HCID 10942334Sodium Methoxide

Product 1

HCID 198211512-Methyl-4-methoxy-5-fluoroacetylaminophenolYield 13.9%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 962WaterSolvent

Procedure

Into 15 ml of benzene were added 2.10 g (13.7 mmol) of 2-methyl-4-methoxy-5-aminophenol, 1.28 g (13.9 mmol, 1.0 eq.) of methyl fluoroacetate and 1.64 g (30.4 mmol) of sodium methoxide and the mixture was heated under reflux for 6.5 hours. After allowing to cool, the mixture was poured into 300 ml of water, and neutralized with acetic acid and extracted with 200 ml of ethyl acetate. The organic layer was washed with a saturated aqueous solution of common salt and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to obtain dark-brown crystals. The crystals were purified by silica gel column chromatography (Silica Gel 60, trade name, manufactured by Merck Co., 70-230 mesh, 200 g, eluent: ethyl acetate) and pale brown solid matters were obtained from the 600-900 ml fraction. The solid matters were recrystallized from the solvent mixture of hexane/ethyl acetate (2:1 by volume) to give 230 mg (1.9 mmol) of 2-methyl-4-methoxy-5-fluoroacetylaminophenol. The yield was 8%.

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 6.5 hours
  3. temperatureto cool
  4. extractionextracted with 200 ml of ethyl acetate
  5. washThe organic layer was washed with a saturated aqueous solution of common salt
  6. dry with materialdried over anhydrous sodium sulfate
  7. distillationThe solvent was distilled off under reduced pressure
  8. customto obtain dark-brown crystals
  9. customThe crystals were purified by silica gel column chromatography (Silica Gel 60, trade name, manufactured by Merck Co., 70-230 mesh, 200 g, eluent: ethyl acetate)
  10. custompale brown solid matters were obtained from the 600-900 ml fraction
  11. customThe solid matters were recrystallized from the solvent mixture of hexane/ethyl acetate (2:1 by volume)

Sources & evidence

ORD record
ord-6c2f16e27b4d4939a721ec34b2c80c96
Source dataset
uspto-grants-1991_05
Patent number
US05015260

Reaction notes

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