Potassium Carbonate → 1-Bromo-4-(3-chloro-4-(trifluoromethyl)benzyloxy)-2,5-difluorobenzene

HRID 508428Notes

Reaction equation

HRID 508428 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[C:10]([F:13])([F:12])[F:11])[CH2:5]Br.[Br:14][C:15]1[C:20]([F:21])=[CH:19][C:18]([OH:22])=[C:17]([F:23])[CH:16]=1.C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[Br:14][C:15]1[CH:16]=[C:17]([F:23])[C:18]([O:22][CH2:5][C:4]2[CH:7]=[CH:8][C:9]([C:10]([F:13])([F:12])[F:11])=[C:2]([Cl:1])[CH:3]=2)=[CH:19][C:20]=1[F:21]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 70180424-Bromo-2,5-difluorophenolHCID 235127654-(Bromomethyl)-2-chloro-1-(trifluoromethyl)benzene

Product 1

HCID 866825541-Bromo-4-(3-chloro-4-(trifluoromethyl)benzyloxy)-2,5-difluorobenzeneYield 99%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

To solution of 3-chloro-4-(trifluoromethyl)benzyl bromide (300 mg, 1.097 mmol) in acetone (15 mL) was added 4-bromo-2,5-difluorophenol (1.097 mmol) followed by potassium carbonate (303 mg, 2.194 mmol). The reaction mixture was heated at reflux for 3.5 hours and then allowed to cool to room temperature. The solvent was removed under reduced pressure to yield a white solid, which was partitioned with water/EtOAc mixture (1:1, 50 mL). The organic layer was separated and the aqueous was extracted with EtOAc (3×30 mL). The combined organics were washed with brine (50 mL), dried over sodium sulphate, filtered and concentrated in vacuo to give the title compound as a white solid (434 mg, 99%).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 3.5 hours
  3. customThe solvent was removed under reduced pressure
  4. customto yield a white solid, which
  5. customwas partitioned with water/EtOAc mixture (1:1, 50 mL)
  6. customThe organic layer was separated
  7. extractionthe aqueous was extracted with EtOAc (3×30 mL)
  8. washThe combined organics were washed with brine (50 mL)
  9. dry with materialdried over sodium sulphate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-e88892a6c818425ea4627e54c290cd81
Source dataset
uspto-grants-2015_08
Patent number
US09096500B2

Reaction notes

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