Bromobenzene → 2,4-Difluoro-1,1'-biphenyl

HRID 221387Notes

Reaction equation

HRID 221387 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1B(O)O.Br[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

7

Reactant 3

HCID 7961BromobenzeneHCID 10340Sodium CarbonateHCID 27343342,4-Difluorophenylboronic acid

Product 1

HCID 1699742,4-Difluoro-1,1'-biphenyl

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
90 °C

Procedure

2,4-Difluorophenylboronic acid (15 g, 129 mmol) was added to a solution of bromobenzene (19.8 g, 126 mmol) in DME (500 mL). To this was added a solution of sodium carbonate (55.8 g, 520 mmol) in water (260 mL). The solution was degassed by bubbling argon through the mixture and then stirred under argon. Pd(dppf)Cl2 (1.5 g, 2.1 mmol) was added and the flask was flushed with argon and heated at 90° C. overnight. The mixture was then cooled to room temperature and water (150 mL) and ethyl acetate (500 mL) were added. The layers were separated and the organic layer washed with 2 M NaOH (100 mL), water (100 mL) and brine (100 mL). The black ethyl acetate layer was dried over MgSO4, charcoal was added, and the mixture was filtered through a short pad of silica. Evaporation of the solvents gave 2,4-difluorobiphenyl as a brown oil, which crystallised on standing (21.2 g).

Workup

  1. customThe solution was degassed
  2. customby bubbling argon through the mixture
  3. customthe flask was flushed with argon
  4. temperatureThe mixture was then cooled to room temperature
  5. additionwater (150 mL) and ethyl acetate (500 mL) were added
  6. customThe layers were separated
  7. washthe organic layer washed with 2 M NaOH (100 mL), water (100 mL) and brine (100 mL)
  8. dry with materialThe black ethyl acetate layer was dried over MgSO4, charcoal
  9. additionwas added
  10. filtrationthe mixture was filtered through a short pad of silica
  11. customEvaporation of the solvents

Sources & evidence

ORD record
ord-1e2b3341fa654e64ab012fc4bfc0d3c5
Source dataset
uspto-grants-2012_06
Patent number
US08207167B2

Reaction notes

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