Sodium Carbonate → Methyl 2-methyl-2'-(trifluoromethyl)biphenyl-4-carboxylate

HRID 2184427Notes

Reaction equation

HRID 2184427 reaction equation
[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][C:7](Br)=[C:6]([CH3:11])[CH:5]=1.[F:13][C:14]([F:25])([F:24])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1>[CH3:1][O:2][C:3]([C:4]1[CH:9]=[CH:8][C:7]([C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=2[C:14]([F:25])([F:24])[F:13])=[C:6]([CH3:11])[CH:5]=1)=[O:12]

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 27343872-(Trifluoromethyl)benzeneboronic acidHCID 3294148Methyl 4-bromo-3-methylbenzoate

Product 1

HCID 59606539Methyl 2-methyl-2'-(trifluoromethyl)biphenyl-4-carboxylateYield 78.1%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 4-bromo-3-methylbenzoic acid methyl ester of Step A (2.0 g, 8.7 mmol), 2-trifluoromethyl-phenyl boronic acid (1.65 g, 8.7 mmol) and sodium carbonate (4.1 g, 38.7 mmol) in toluene:ethanol:water (50 mL:25 mL: 25 mL) was purged with nitrogen for 1 hour. After addition of the tetrakis(triphenylphosphine) palladium(0) catalyst (0.50 g, 0.43 mmol, the reaction was heated at 100° C. overnight. The cooled reaction mixture was filtered through Celite and the cake washed with ethyl acetate. The organic layer was washed with water, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give a brown oil. Purification by flash chromatography with a solvent gradient of 25% to 50% dichloromethane in hexane provided 2.0 g of the title compound as a colorless oil.

Workup

  1. customethanol:water (50 mL:25 mL: 25 mL) was purged with nitrogen for 1 hour
  2. additionAfter addition of the tetrakis(triphenylphosphine) palladium(0) catalyst (0.50 g, 0.43 mmol
  3. customThe cooled reaction mixture
  4. filtrationwas filtered through Celite
  5. washthe cake washed with ethyl acetate
  6. washThe organic layer was washed with water
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customto give a brown oil
  11. customPurification by flash chromatography with a solvent gradient of 25% to 50% dichloromethane in hexane

Sources & evidence

ORD record
ord-faa26f9e31d94604851095c8bacda710
Source dataset
uspto-grants-2005_05
Patent number
US06900200B2

Reaction notes

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