O-Cresol → 4-Methoxy-3-o-tolyloxy-benzoic acid

HRID 2094729Notes

Reaction equation

HRID 2094729 reaction equation
C(=O)([O-])[O-].[K+].[K+].[C:7]1([CH3:14])[C:12]([OH:13])=[CH:11][CH:10]=[CH:9][CH:8]=1.Br[C:16]1[CH:17]=[C:18]([CH:22]=[CH:23][C:24]=1[O:25][CH3:26])[C:19]([OH:21])=[O:20]>CN(C=O)C.[Cu]>[CH3:26][O:25][C:24]1[CH:23]=[CH:22][C:18]([C:19]([OH:21])=[O:20])=[CH:17][C:16]=1[O:13][C:12]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[CH3:14]

Participants

6

Reactant 3

HCID 335O-Cresol2×HCID 11430Potassium Carbonate2×HCID 668363-Bromo-4-methoxybenzoic acid

Product 1

HCID 670766834-Methoxy-3-o-tolyloxy-benzoic acidYield 53.7%

Reagents, catalysts & solvents 2

HCID 23978CopperCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
165 °C

Procedure

Potassium carbonate (1.20 g, 8.66 mmol), o-cresol (468 mg, 4.33 mmol), copper powder (28 mg, 0.43 mmol) and 3-bromo-4-methoxybenzoic acid (1.00 g, 4.33 mmol) were suspended in DMF (5 ml) and heated to 165° C. overnight. Potassium carbonate (1.20 g, 8.66 mmol) and o-cresol (468 mg, 4.33 mmol) were added once again and heating was continued for another 2 h. The crude mixture was partitioned between EA and 2 N hydrochloric acid, the aqueous phase extracted with EA, and the combined organic phases were dried over magnesium sulfate, filtered and evaporated to dryness. The residue was purified by silica gel chromatography (HEP/EA gradient) to yield 600 mg of the title compound.

Workup

  1. temperatureheating
  2. customThe crude mixture was partitioned between EA and 2 N hydrochloric acid
  3. extractionthe aqueous phase extracted with EA
  4. dry with materialthe combined organic phases were dried over magnesium sulfate
  5. filtrationfiltered
  6. customevaporated to dryness
  7. customThe residue was purified by silica gel chromatography (HEP/EA gradient)

Sources & evidence

ORD record
ord-883c9a427e8e4dabab417be27a4247c3
Source dataset
uspto-grants-2013_05
Patent number
US08445530B2

Reaction notes

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