Sodium Carbonate → 3',4'-Dichloro-2-fluoro-4-methyl-biphenyl

HRID 658507Notes

Reaction equation

HRID 658507 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH3:9])[CH:5]=[CH:6][C:7]=1Br.[Cl:10][C:11]1[CH:12]=[C:13](B(O)O)[CH:14]=[CH:15][C:16]=1[Cl:17].C(=O)([O-])[O-].[Na+].[Na+]>C(O)C.[Pd]>[Cl:10][C:11]1[CH:12]=[C:13]([C:7]2[CH:6]=[CH:5][C:4]([CH3:9])=[CH:3][C:2]=2[F:1])[CH:14]=[CH:15][C:16]=1[Cl:17]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 5732804-Bromo-3-fluorotolueneHCID 27343303,4-Dichlorobenzeneboronic acid

Product 1

HCID 669167363',4'-Dichloro-2-fluoro-4-methyl-biphenyl

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Conditions

Temperature
40 °C

Procedure

3-fluoro-4-bromotoluene (50 g, 0.265 mol) and 3,4-dichlorophenylboronic acid (53 g, 0.278 mol) were dissolved in ethanol (970 ml) and sodium carbonate (56.1 g, 0.529 mol) was added. Palladium 10% on charcoal (6.6 g) was added, and the mixture was refluxed for 4 hours under nitrogen atmosphere. The reaction mixture was cooled, filtered and concentrated, isopropyl acetate (250 ml) was added, and then the solution was concentrated again. The residue was dissolved in isopropyl acetate (250 ml) and 1M sodium hydroxide (250 ml). The organic phase was separated, washed with water (125 ml), neutralized with hydrogen chloride 3 M, washed with brine (250 ml), and concentrated. The residue was mixed with acetonitrile/water 1/1 v/v (150 ml), heated to 40° C. to dissolve and then cooled to 0 to 5° C., and stirred for 30 minutes at this temperature. The compound 3′,4′-dichloro-2-fluoro-4-methyl-biphenyl crystallized as a powder.

Workup

  1. temperaturethe mixture was refluxed for 4 hours under nitrogen atmosphere
  2. temperatureThe reaction mixture was cooled
  3. filtrationfiltered
  4. concentrationconcentrated
  5. additionisopropyl acetate (250 ml) was added
  6. concentrationthe solution was concentrated again
  7. dissolutionThe residue was dissolved in isopropyl acetate (250 ml)
  8. customThe organic phase was separated
  9. washwashed with water (125 ml)
  10. washwashed with brine (250 ml)
  11. concentrationconcentrated
  12. additionThe residue was mixed with acetonitrile/water 1/1 v/v (150 ml)
  13. dissolutionto dissolve
  14. temperaturecooled to 0 to 5° C.
  15. customThe compound 3′,4′-dichloro-2-fluoro-4-methyl-biphenyl crystallized as a powder

Sources & evidence

ORD record
ord-c83d7449d98a4445bbf4c90d35771c0e
Source dataset
uspto-grants-2011_12
Patent number
US08076505B2

Reaction notes

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