Sodium Carbonate → (2-{Difluoro-[4'-(trifluoromethyl)biphenyl-4-yl]methoxy}-5-fluorophenyl)methanol

HRID 1672638Notes

Reaction equation

HRID 1672638 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:20])([F:19])[O:9][C:10]2[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=2[CH2:17][OH:18])=[CH:4][CH:3]=1.[F:21][C:22]([F:33])([F:32])[C:23]1[CH:28]=[CH:27][C:26](B(O)O)=[CH:25][CH:24]=1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[F:19][C:8]([F:20])([C:5]1[CH:6]=[CH:7][C:2]([C:26]2[CH:27]=[CH:28][C:23]([C:22]([F:33])([F:32])[F:21])=[CH:24][CH:25]=2)=[CH:3][CH:4]=1)[O:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=1[CH2:17][OH:18]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 27343894-(Trifluoromethyl)phenylboronic acidHCID 57864347{2-[(4-Bromophenyl)(difluoro)methoxy]-5-fluorophenyl}methanol

Product 1

HCID 57864335(2-{Difluoro-[4'-(trifluoromethyl)biphenyl-4-yl]methoxy}-5-fluorophenyl)methanolYield 85%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

473 mg (1.36 mmol) of {2-[(4-bromophenyl)(difluoro)methoxy]-5-fluorophenyl}methanol from Example 39A are dissolved in 8 ml of 1,2-dimethoxyethane and, under argon, 362.6 mg (1.91 mmol) of 4-trifluoromethylphenylboronic acid, 67 mg of bis(triphenylphosphine)-palladium(II) chloride and 1.5 ml of a 2 M solution of sodium carbonate in water are added. The reaction mixture is then stirred under reflux for 12 hours. The mixture is subsequently cooled, filtered through 5 g of Celite, washed with dichloromethane and concentrated. The resulting crude product is purified by silica gel chromatography (mobile phase: cyclohexane/ethyl acetate 10:1). 532 mg (1.29 mmol, 90% purity, 85% yield) of a colorless oil are obtained.

Workup

  1. temperatureunder reflux for 12 hours
  2. temperatureThe mixture is subsequently cooled
  3. filtrationfiltered through 5 g of Celite
  4. washwashed with dichloromethane
  5. concentrationconcentrated
  6. customThe resulting crude product is purified by silica gel chromatography (mobile phase: cyclohexane/ethyl acetate 10:1)
  7. custom532 mg (1.29 mmol, 90% purity, 85% yield) of a colorless oil are obtained

Sources & evidence

ORD record
ord-abea5a68cafa44c699033a18140973fb
Source dataset
uspto-grants-2011_08
Patent number
US07998988B2

Reaction notes

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