Ethanol → 3',4-Difluoro-[1,1'-biphenyl]-3-carboxylic acid

HRID 1528010Notes

Reaction equation

HRID 1528010 reaction equation
[F:1][C:2]1[CH:3]=[C:4](B(O)O)[CH:5]=[CH:6][CH:7]=1.Br[C:12]1[CH:13]=[CH:14][C:15]([F:21])=[C:16]([CH:20]=1)[C:17]([OH:19])=[O:18].C(=O)([O-])[O-].[Cs+].[Cs+].C(O)C>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.C1(C)C=CC=CC=1>[F:1][C:2]1[CH:3]=[C:4]([C:12]2[CH:13]=[CH:14][C:15]([F:21])=[C:16]([C:17]([OH:19])=[O:18])[CH:20]=2)[CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 702EthanolHCID 10796Cesium carbonateHCID 27339863-Fluorophenylboronic acidHCID 27363155-Bromo-2-fluorobenzoic acid

Product 1

HCID 463123323',4-Difluoro-[1,1'-biphenyl]-3-carboxylic acid

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

A 50 mL Schlenk tube was charged with (3-fluorophenyl)boronic acid (140 mg, 1.0 mmol), 5-bromo-2-fluorobenzoic acid (263 mg, 1.2 mmol), tetrakis(triphenylphosphine)palladium (0) (58 mg, 0.05 mmol) and cesium carbonate (1.3 g, 4.0 mmol). Ethanol (5 mL) and toluene (5 mL) were added and the tube was sealed and heated at 80° C. for 3 h. The cooled mixture was transferred to a flask, washing with ethanol, and concentrated in vacuo. The residue was diluted with water (10 mL) and extracted with EtOAc (2×10 mL). The aqueous phase was acidified with 1.0 N aqueous HCl (10 mL) and extracted with EtOAc (3×10 mL). The extracts were dried (Na2SO4), filtered and concentrated in vacuo. 1H-NMR showed the desired product, 3′,4-difluoro-[1,1′-biphenyl]-3-carboxylic acid, was slightly contaminated with 2-fluorobenzoic acid. The impure product (215 mg, ˜92%) was used without further purification.

Workup

  1. customthe tube was sealed
  2. customThe cooled mixture was transferred to a flask
  3. washwashing with ethanol
  4. concentrationconcentrated in vacuo
  5. additionThe residue was diluted with water (10 mL)
  6. extractionextracted with EtOAc (2×10 mL)
  7. extractionextracted with EtOAc (3×10 mL)
  8. dry with materialThe extracts were dried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe impure product (215 mg, ˜92%) was used without further purification

Sources & evidence

ORD record
ord-e17ba03d914e4f2489dd1bc8a3cd1a26
Source dataset
uspto-grants-2015_07
Patent number
US09090584B2

Reaction notes

Loading…