2-Bromobenzonitrile → 2-(2-Fluorophenyl)benzonitrile

HRID 2183918Notes

Reaction equation

HRID 2183918 reaction equation
Br[C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1[C:4]#[N:5].[F:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1B(O)O.[F-].[K+].C(P(C(C)(C)C)C(C)(C)C)(C)(C)C>O1CCCC1.O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[C:2]1[C:3]([C:4]#[N:5])=[CH:6][CH:7]=[CH:8][CH:9]=1

Participants

8

Reactant 4

HCID 162722-BromobenzonitrileHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 522689Potassium FluorideHCID 27343542-Fluorophenylboronic acid

Product 1

HCID 13933962-(2-Fluorophenyl)benzonitrileYield 100%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 2-bromobenzonitrile (5.1 g, 28 mmol), 2-fluorobenzeneboronic acid (4.9 g, 35 mmol) and potassium fluoride (5.37 g, 92 mmol) in tetrahydrofuran (50 ml) was degassed with nitrogen for 10 min. This mixture was then treated with tris(dibenzylideneacetone)dipalladium(0) (510 mg, 0.56 mmol) followed by tri-tert-butylphosphine (5.6 ml of a 0.2M solution in 1,4-dioxane, 1.12 mmol) and the reaction was stirred at ambient temperature for 15 min. The resulting slurry was then heated at 50° C. for 30 min in order to consume remaining starting materials and then cooled to ambient temperature. The reaction mixture was filtered, washing the filter-cake with tetrahydrofuran (50 ml). The filtrate was evaporated to dryness and the residue partitioned between ethyl acetate and water. The organics were washed with brine, dried over anhydrous magnesium sulfate, filtered and pre-adsorbed onto silica. Purification by chromatography on silica eluting with isohexane on a gradient of ethyl acetate (5-10%) gave 2′-fluorobiphenyl-2-carbonitrile as a pale yellow solid (5.5 g, 100%): δH (360 MHz, CDCl3) 7.19-7.29 (2H, m), 7.40-7.52 (4H, m), 7.65 (1H, ddd, J 8, 8 and 1), 7.79 (1H, dd, J 8 and 1).

Workup

  1. customwas degassed with nitrogen for 10 min
  2. temperatureThe resulting slurry was then heated at 50° C. for 30 min in order
  3. customto consume
  4. temperaturecooled to ambient temperature
  5. filtrationThe reaction mixture was filtered
  6. washwashing the
  7. filtrationfilter-cake with tetrahydrofuran (50 ml)
  8. customThe filtrate was evaporated to dryness
  9. customthe residue partitioned between ethyl acetate and water
  10. washThe organics were washed with brine
  11. dry with materialdried over anhydrous magnesium sulfate
  12. filtrationfiltered and pre-adsorbed onto silica
  13. customPurification by chromatography on silica eluting with isohexane on a gradient of ethyl acetate (5-10%)

Sources & evidence

ORD record
ord-7be29a11ce9c4fc4af84dcbde8f38ed5
Source dataset
uspto-grants-2005_05
Patent number
US06900215B2

Reaction notes

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