4-Bromophenol → 2-(4-Bromophenoxy)-5-methoxybenzoic acid

HRID 1851631Notes

Reaction equation

HRID 1851631 reaction equation
Br[C:2]1[CH:10]=[CH:9][C:8]([O:11][CH3:12])=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[Br:13][C:14]1[CH:19]=[CH:18][C:17]([OH:20])=[CH:16][CH:15]=1.C(=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C>C1(C)C=CC=CC=1>[Br:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][C:2]2[CH:10]=[CH:9][C:8]([O:11][CH3:12])=[CH:7][C:3]=2[C:4]([OH:6])=[O:5])=[CH:16][CH:15]=1

Participants

6

Reactant 4

HCID 78084-BromophenolHCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 899062-Bromo-5-methoxybenzoic acid

Product 1

HCID 574756322-(4-Bromophenoxy)-5-methoxybenzoic acid

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A RBF equipped with a reflux condenser was charged with 2-bromo-5-methoxy benzoic acid (430 g, 1.8614 mol), 4-bromo phenol (322 g, 1.8614 mol, 1 eq), potassium carbonate (514.5 g, 3.7 228 mol, 2.0 eq) and CuOTf-toluene complex (24.08 g, 0.04653 mol, 0.025 eq). Ethyl acetate (9.0 ml 0.09679 mol, 0.052) and toluene (1.3 L) was carefully added portion wise. After stirring at RT for 10 min, the mixture was heated to 50° C. and stirred for 30 min. The mixture was then heated to 110° C. for 20 hrs. The reaction was monitored by TLC. After 20 hrs, TLC showed total consumption of starting materials. The reaction mixture was cooled to RT, diluted with water and acidified by 2N HCl. The reaction mixture was extracted with ethyl acetate (3.0×2 liter) followed by filteration of the extract through celite bed and washing with ethyl acetate (1.0 liter). Combined extracts were dried over sodium sulfate and concentrated to yield a crude mass of 590 g. (Dark brown solid). This mass was used directly in step 2.

Workup

  1. customA RBF equipped with a reflux condenser
  2. temperaturethe mixture was heated to 50° C.
  3. stirringstirred for 30 min
  4. temperatureThe mixture was then heated to 110° C. for 20 hrs
  5. waitAfter 20 hrs
  6. customconsumption of starting materials
  7. temperatureThe reaction mixture was cooled to RT
  8. additiondiluted with water
  9. extractionThe reaction mixture was extracted with ethyl acetate (3.0×2 liter)
  10. extractionextract through celite bed
  11. washwashing with ethyl acetate (1.0 liter)
  12. dry with materialCombined extracts were dried over sodium sulfate
  13. concentrationconcentrated
  14. customto yield a crude mass of 590 g

Sources & evidence

ORD record
ord-fd146bc4dee84d3794b6b89f0e633711
Source dataset
uspto-grants-2015_02
Patent number
US08957083B2

Reaction notes

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