Methanol → 2-Methyl-6-phenoxy-benzoic acid

HRID 2077148Notes

Reaction equation

HRID 2077148 reaction equation
Cl[C:2]1[CH:10]=[CH:9][CH:8]=[C:7]([CH3:11])[C:3]=1[C:4]([OH:6])=[O:5].[C:12]1([OH:18])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.CO>C[O-].[Na+].[Cu]>[CH3:11][C:7]1[CH:8]=[CH:9][CH:10]=[C:2]([O:18][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:3]=1[C:4]([OH:6])=[O:5]

Participants

6

Reactant 3

HCID 887MethanolHCID 996PhenolHCID 888702-Chloro-6-methylbenzoic acid

Product 1

HCID 671100872-Methyl-6-phenoxy-benzoic acidYield 66.4%

Reagents, catalysts & solvents 2

HCID 23978CopperCatalystHCID 10942334Sodium MethoxideSolvent

Procedure

2-Chloro-6-methyl-benzoic acid (30 mmol, 5.22 g) and phenol (40 mmol, 3.8 g) were dissolved in a solution of NaOMe (30 wt %) in MeOH (ca. 66 mmol, 12 mL). To the solution was added copper bronze (3 mmol, 193 mg) before it was concentrated in vacuo. Then, 1,2-dichlorobenzene (24 mL) was added and the mixture was refluxed under nitrogen for 2 h with stirring. After cooling to ambient temperature water (200 mL) and Et2O (150 mL) were added and the mixture was stirred vigorously for 30 min before the organic phase was separated and discarded. The aqueous phase was washed with Et2O (150 mL) before it was acidified by addition of 5 N hydrochloric acid. The resulting mixture was extracted with ethyl acetate (1×100 mL). The organic phase was dried over MgSO4 and concentrated in vacuo. The residue was recrystallized from hexanes/toluene to give the title compound as a tan solid (4.55 g); MS-(−)-ion: M−1=226.8.

Workup

  1. concentrationwas concentrated in vacuo
  2. additionThen, 1,2-dichlorobenzene (24 mL) was added
  3. temperaturethe mixture was refluxed under nitrogen for 2 h
  4. additionwere added
  5. stirringthe mixture was stirred vigorously for 30 min before the organic phase
  6. customwas separated
  7. washThe aqueous phase was washed with Et2O (150 mL) before it
  8. additionwas acidified by addition of 5 N hydrochloric acid
  9. extractionThe resulting mixture was extracted with ethyl acetate (1×100 mL)
  10. dry with materialThe organic phase was dried over MgSO4
  11. concentrationconcentrated in vacuo
  12. customThe residue was recrystallized from hexanes/toluene

Sources & evidence

ORD record
ord-b4785e95128f4cb2bc1c8e7537ab8529
Source dataset
uspto-grants-2011_04
Patent number
US07928120B2

Reaction notes

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