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

HRID 2170019Notes

Reaction equation

HRID 2170019 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+].C(OCC)(=O)C>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

8

Reactant 4

HCID 7961BromobenzeneHCID 8857Ethyl AcetateHCID 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 962WaterSolvent2×HCID 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 mixture heated overnight at 90° C. under argon. The mixture was cooled to room temperature and water (150 mL) and ethyl acetate (500 mL) were added. The layers were separated and the organic layer was 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. temperatureThe mixture was cooled to room temperature
  4. customThe layers were separated
  5. washthe organic layer was washed with 2 M NaOH (100 mL), water (100 mL) and brine (100 mL)
  6. dry with materialThe black ethyl acetate layer was dried over MgSO4, charcoal
  7. additionwas added
  8. filtrationthe mixture was filtered through a short pad of silica
  9. customEvaporation of the solvents

Sources & evidence

ORD record
ord-c0c8091855d94e51a7ced9c3cc2d82d5
Source dataset
uspto-grants-2015_06
Patent number
US09050329B1

Reaction notes

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