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

HRID 1830044Notes

Reaction equation

HRID 1830044 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.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)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

6

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 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 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. customThe cooled reaction mixture
  3. filtrationwas filtered through Celite
  4. washthe cake washed with ethyl acetate
  5. washThe organic layer was washed with water
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto give a brown oil
  10. customPurification by flash chromatography with a solvent gradient of 25% to 50% dichloromethane in hexane

Sources & evidence

ORD record
ord-79e9b3744dc04f388ecdb785b194bdcb
Source dataset
uspto-grants-2006_06
Patent number
US07064120B2

Reaction notes

Loading…