Toluene → 5-Formyl-4'-methylbiphenyl-3-carboxylic acid

HRID 1845339Notes

Reaction equation

HRID 1845339 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([CH:11]=[O:12])[CH:10]=1)[C:5]([OH:7])=[O:6].B(O)(O)[C:14]1[CH:15]=[CH:16][C:17]([CH3:20])=[CH:18][CH:19]=1.C1(C)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>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.O>[CH:11]([C:9]1[CH:8]=[C:4]([C:5]([OH:7])=[O:6])[CH:3]=[C:2]([C:14]2[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][CH:15]=2)[CH:10]=1)=[O:12]

Participants

7

Reactant 4

HCID 1140TolueneHCID 10796Cesium carbonateHCID 79799Tolylboronic acidHCID 223207963-Bromo-5-formylbenzoic acid

Product 1

HCID 581880045-Formyl-4'-methylbiphenyl-3-carboxylic acidYield 57.2%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Procedure

To a mixture of 3-bromo-5-formylbenzoic acid (8.0 g, 34.9 mmol), p-tolylboronic acid (9.5 g, 70 mmol), toluene (300 mL), cesium carbonate (28 g, 87 mmol), and water (25 mL) under nitrogen was added tetrakis(triphenylphosphine)palladium(0) (2.0 g, 1.7 mmol). The mixture was heated under reflux for 5 h. After cooling, the mixture was filtered through Celite and the filter cake was washed with EtOAc. The filtrate was washed with brine, dried, and concentrated. The residue was purified by column chromatography using methylene chloride:methanol gradient (0-5%) to afford the title compound (4.8 g, 51%). LC-MS: 239.0 [M−1]−.

Workup

  1. temperatureThe mixture was heated
  2. temperatureunder reflux for 5 h
  3. temperatureAfter cooling
  4. filtrationthe mixture was filtered through Celite
  5. washthe filter cake was washed with EtOAc
  6. washThe filtrate was washed with brine
  7. customdried
  8. concentrationconcentrated
  9. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-d264493ca37e4d6481c079debc6de78c
Source dataset
uspto-grants-2015_02
Patent number
US08946439B2

Reaction notes

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