1,3-Dibromo-5-fluorobenzene → 3'-Bromo-4,5'-difluorobiphenyl-2-carbonitrile

HRID 1180258Notes

Reaction equation

HRID 1180258 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5](B2OC(C)(C)C(C)(C)O2)=[C:6]([CH:9]=1)[C:7]#[N:8].[Br:19][C:20]1[CH:25]=[C:24]([F:26])[CH:23]=[C:22](Br)[CH:21]=1>COCCOC>[Br:19][C:20]1[CH:21]=[C:22]([C:5]2[C:6]([C:7]#[N:8])=[CH:9][C:2]([F:1])=[CH:3][CH:4]=2)[CH:23]=[C:24]([F:26])[CH:25]=1

Participants

4

Reactant 2

HCID 1370031,3-Dibromo-5-fluorobenzeneHCID 221807905-Fluoro-2-(tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile

Product 1

HCID 179648413'-Bromo-4,5'-difluorobiphenyl-2-carbonitrileYield 9.4%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
65 °C

Procedure

5-Fluoro-2-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzonitrile (0.99 g, 4.0 mmol) and 1,3-dibromo-5-fluorobenzene (1.52 g, 6.0 mmol) were suspended in 1,2-dimethoxyethane (8 ml) and 2N sodium carbonate solution (4 ml) and degassed for 30 min before addition of tetrakis(triphenylphosphine)palladium(0). On complete addition the mixture was heated at 65° C. for 20 h. The mixture was partitioned between ethyl acetate (100 ml) and water (50 ml), the organic layer separated and washed with brine (50 ml), dried over anhydrous sodium sulphate, filtered and evaporated onto silica. The product was purified by flash column chromatography on silica, eluting with isohexane on a gradient of diethyl ether (5-100%). Combination of the desired fractions and evaporation gave 3′-bromo-4,5′-difluorobiphenyl-2-carbonitrile (110 mg, 9%) as a white solid: δH (500 Mfz, CDCl3) 7.53-7.55 (1H, m), 7.67 (1H, s), 7.69-7.76 (3H, m), 8.03 (1H, dd, J 9 and 2).

Workup

  1. custom2N sodium carbonate solution (4 ml) and degassed for 30 min before addition of tetrakis(triphenylphosphine)palladium(0)
  2. additionOn complete addition the mixture
  3. customThe mixture was partitioned between ethyl acetate (100 ml) and water (50 ml)
  4. customthe organic layer separated
  5. washwashed with brine (50 ml)
  6. dry with materialdried over anhydrous sodium sulphate
  7. filtrationfiltered
  8. customevaporated onto silica
  9. customThe product was purified by flash column chromatography on silica
  10. washeluting with isohexane on a gradient of diethyl ether (5-100%)
  11. customCombination of the desired fractions and evaporation

Sources & evidence

ORD record
ord-e27e468424f041a391795dfdd250d5e1
Source dataset
uspto-grants-2007_10
Patent number
US07279580B2

Reaction notes

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