Potassium Carbonate → 3-(3-Fluorophenyl)-5-fluorobenzoic acid

HRID 1528011Notes

Reaction equation

HRID 1528011 reaction equation
[F:1][C:2]1[CH:3]=[C:4](B(O)O)[CH:5]=[CH:6][CH:7]=1.Cl[C:12]1[CH:13]=[C:14]([CH:18]=[C:19]([F:21])[CH:20]=1)[C:15]([OH:17])=[O:16].C(=O)([O-])[O-].[K+].[K+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.[Na+].O.C1(P(C2CCCCC2)C2(OC)C(S([O-])(=O)=O)C=CC(OC)=C2C2C=CC=CC=2)CCCCC1>[F:1][C:2]1[CH:3]=[C:4]([C:12]2[CH:20]=[C:19]([F:21])[CH:18]=[C:14]([C:15]([OH:17])=[O:16])[CH:13]=2)[CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 27339863-Fluorophenylboronic acidHCID 27348403-Chloro-5-fluorobenzoic acid

Product 1

HCID 463123233-(3-Fluorophenyl)-5-fluorobenzoic acidYield 100.3%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 866560822-Dicyclohexylphosphino-2,6-dimethoxy-3-sulfonato-1,1'-biphenyl hydrate sodium saltCatalyst

Procedure

A 2 dram vial was charged with (3-fluorophenyl)boronic acid (168 mg, 1.2 mmol), 3-chloro-5-fluorobenzoic acid (175 mg, 1.0 mmol), potassium carbonate (345 mg, 2.5 mmol), palladium acetate (1.1 mg, 0.005 mmol) and 2-dicyclohexylphosphino-2,6-dimethoxy-3-sulfonato-1,1′-biphenyl hydrate sodium salt (5 mg, 0.01 mmol). The vial was fitted with a septum cap, degassed water (1.5 mL) was added and the mixture was purged with nitrogen and stirred at room temperature. After stirring for 4 d, the mixture was diluted with water (30 mL), acidified to pH 4 with 1.0 N aqueous HCl and extracted with EtOAc (3×25 mL). The combined extracts were dried (Na2SO4), filtered and concentrated in vacuo to afford 235 mg (quant.) of 3′,5-difluoro-[1,1′-biphenyl]-3-carboxylic acid which was used without further purification.

Workup

  1. customThe vial was fitted with a septum
  2. customcap
  3. customdegassed water (1.5 mL)
  4. additionwas added
  5. customthe mixture was purged with nitrogen
  6. stirringAfter stirring for 4 d
  7. additionthe mixture was diluted with water (30 mL)
  8. extractionextracted with EtOAc (3×25 mL)
  9. dry with materialThe combined extracts were dried (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ccbab59478fb468eb517b34e84d28e51
Source dataset
uspto-grants-2015_07
Patent number
US09090584B2

Reaction notes

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