Sodium Carbonate → 3'-Methyl-biphenyl-4-carboxylic acid ethyl ester

HRID 2375149Notes

Reaction equation

HRID 2375149 reaction equation
[CH2:1]([O:3][C:4](=[O:12])[C:5]1[CH:10]=[CH:9][C:8](Br)=[CH:7][CH:6]=1)[CH3:2].[CH3:13][C:14]1[CH:15]=[C:16](B(O)O)[CH:17]=[CH:18][CH:19]=1.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>[CH2:1]([O:3][C:4]([C:5]1[CH:10]=[CH:9][C:8]([C:18]2[CH:17]=[CH:16][CH:15]=[C:14]([CH3:13])[CH:19]=2)=[CH:7][CH:6]=1)=[O:12])[CH3:2]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 22043Ethyl 4-bromobenzoateHCID 27339503-Tolylboronic acid

Product 1

HCID 208200733'-Methyl-biphenyl-4-carboxylic acid ethyl esterYield 87.3%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 4-bromo benzoic acid ethyl ester (2.7 mL, 16.5 mmol), 3-methyl phenylboronic acid (2.2 g, 16.2 mmol) and sodium carbonate (7.5 g, 70.8 mmol) in toluene:ethanol:water (75 mL:37 mL:37 mL), was flushed with nitrogen for 1 hour. After addition of the tetrakis(triphenylphosphine) palladium(0) catalyst (0.94 g, 0.81 mmol), the reaction was heated at 100° C. overnight. After cooling, the mixture was filtered through Celite which was then 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 of the residue by flash chromatography with a solvent gradient from 25% to 50% of dichloromethane in hexane provided the title compound (3.4 g, 87.3%) as a colorless oil.

Workup

  1. customethanol:water (75 mL:37 mL:37 mL), was flushed with nitrogen for 1 hour
  2. temperatureAfter cooling
  3. filtrationthe mixture was filtered through Celite which
  4. washwas then 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 of the residue by flash chromatography with a solvent gradient from 25% to 50% of dichloromethane in hexane

Sources & evidence

ORD record
ord-bd5b2327015d40cb917c586b09fb6a13
Source dataset
uspto-grants-2008_12
Patent number
US07465722B2

Reaction notes

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