Phenylboronic Acid → 5-(Trifluoromethyl)biphenyl-2-carboxylic acid

HRID 560212Notes

Reaction equation

HRID 560212 reaction equation
Br[C:2]1[CH:10]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[C:15]1(B(O)O)[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1>O1CCOCC1.C(=O)([O-])[O-].[Na+].[Na+].C(OCC)(=O)C.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:12][C:11]([F:14])([F:13])[C:9]1[CH:10]=[C:2]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:3]([C:4]([OH:6])=[O:5])=[CH:7][CH:8]=1

Participants

9

Reactant 3

HCID 66827Phenylboronic AcidHCID 676052-Bromo-4-(trifluoromethyl)benzoic acidHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenyl

Product 1

HCID 463151975-(Trifluoromethyl)biphenyl-2-carboxylic acidYield 64%

Reagents, catalysts & solvents 5

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 10340Sodium CarbonateSolvent2×HCID 312751,4-DioxaneSolvent

Procedure

2-Bromo-4-trifluoromethyl-benzoic acid (100 mg, 0.372 mmol) and phenylboronic acid (70 mg, 0.574 mmol) were dissolved in 6 mL dioxane and 3 mL 1N sodium carbonate solution. The mixture was evacuated and back-filled with argon several times to remove oxygen. 2-Dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl (S-Phos, 31 mg, 0.075 mmol) and palladium acetate (8 mg, 0.036 mmol) were added and the reaction mixture was refluxed overnight. The mixture was diluted with ethyl acetate, water and 2N sodium carbonate solution. The mixture was extracted three times with 2N sodium carbonate solution and the aqueous layers washed with ethyl acetate. The combined organic layers were discarded. The combined aqueous layers were acidified with 2N HCl and extracted twice with dichloromethane. The organic layers were washed with brine, combined, dried over sodium sulfate, filtered and concentrated down. Purification of the residue by flash chromatography on gel with dichloromethane/methanol/acetic acid (100:0:0→90:10:0.5) yielded the title compound as a white solid (63 mg, 64%).

Workup

  1. customThe mixture was evacuated
  2. additionback-filled with argon several times
  3. customto remove oxygen
  4. temperaturethe reaction mixture was refluxed overnight
  5. extractionThe mixture was extracted three times with 2N sodium carbonate solution
  6. washthe aqueous layers washed with ethyl acetate
  7. extractionextracted twice with dichloromethane
  8. washThe organic layers were washed with brine
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated down
  12. customPurification of the residue by flash chromatography on gel with dichloromethane/methanol/acetic acid (100:0:0→90:10:0.5)

Sources & evidence

ORD record
ord-e7105b84f02b48c29515306a11f84846
Source dataset
uspto-grants-2011_11
Patent number
US08063098B2

Reaction notes

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