Water → Methyl 2'-methyl-2-(trifluoromethyl)-[1,1'-biphenyl]-4-carboxylate

HRID 572537Notes

Reaction equation

HRID 572537 reaction equation
Br[C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=1[C:12]([F:15])([F:14])[F:13].[C:16]1([CH3:25])[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1B(O)O.C(=O)([O-])[O-].[K+].[K+].O>C1(C)C=CC=CC=1.CCOC(C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:25][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=1[C:12]([F:15])([F:14])[F:13]

Participants

8

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 27332672-Methylphenyl boronic acidHCID 10891333Methyl 4-bromo-3-(trifluoromethyl)benzoate

Product 1

HCID 58554190Methyl 2'-methyl-2-(trifluoromethyl)-[1,1'-biphenyl]-4-carboxylateYield 103.6%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Methyl 4-bromo-3-(trifluoromethyl)benzoate (6 g; 21 mmol), o-tolylboronic acid (3.2 g; 23 mmol), potassium carbonate (14.7 g; 106 mmol), tetrakis(triphenylphosphine)palladium(0) (2.5 g; 2.12 mmol) were taken up in toluene (30 mL) and water (30 mL) under N2 atmosphere. The reaction mixture was purged with vacuum for 5 minutes, then degassed with N2 and then refluxed for 3 hours. The reaction mixture was cooled to RT, filtered over a pad of celite and washed with toluene (200 mL). The filtrate was concentrated, affording a brown oil which was taken in EtOAc (200 mL). The organic layer was washed with a saturated aqueous solution of NaHCO3 solution (50 mL), water (50 mL) and brine (50 mL), dried over MgSO4 and concentrated affording the title compound as a brown oil (6.4 g, quantitative). HPLC (Method A) Rt 5.33 min (Purity: 60.0%).

Workup

  1. customThe reaction mixture was purged with vacuum for 5 minutes
  2. customdegassed with N2
  3. temperaturerefluxed for 3 hours
  4. filtrationfiltered over a pad of celite
  5. washwashed with toluene (200 mL)
  6. concentrationThe filtrate was concentrated
  7. customaffording a brown oil which
  8. washThe organic layer was washed with a saturated aqueous solution of NaHCO3 solution (50 mL), water (50 mL) and brine (50 mL)
  9. dry with materialdried over MgSO4
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-15d1f61e2bc74c118fe0560364c928c0
Source dataset
uspto-grants-2015_05
Patent number
US09029405B2

Reaction notes

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