Toluene → 2-Cyano-3-fluorobiphenyl

HRID 1882762Notes

Reaction equation

HRID 1882762 reaction equation
Br[C:2]1[CH:9]=[CH:8][CH:7]=[C:6]([F:10])[C:3]=1[C:4]#[N:5].[C:11]1(B(O)O)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.C1(C)C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CO>[F:10][C:6]1[CH:7]=[CH:8][CH:9]=[C:2]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[C:3]=1[C:4]#[N:5]

Participants

7

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 66827Phenylboronic AcidHCID 27831392-Bromo-6-fluorobenzonitrile

Product 1

HCID 235096522-Cyano-3-fluorobiphenyl

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 887MethanolSolvent

Procedure

The compound, 2-Bromo-6-fluorobenzonitrile, the procedure for the preparation of which may be found in Hynes, John B. et. al., J. Hetercycl. Chem. 1988, 25, 1173-7, (2.0 g, 10.0 mmol) and phenylboronic acid (3.66 g, 30 mmol) were added to a mixture of toluene (80 mL), methanol (20 mL), and 2 M aqueous sodium carbonate (20 mL). This mixture was refluxed while stirring under argon for 15 min. The resulting mixture was cooled to room temperature and tetrakis(triphenylphosphine)palladium(0) (1.16 g, 1 mmol) was added. The resulting mixture was then refluxed for 12 hours while stirring under argon. The solvent was removed in vacuo and the residue was partitioned between ethyl acetate and water. The organic phase was washed with water (2×), brine (1×), dried over anhydrous Na2SO4, filtered, and evaporated to give the crude product which was then chromatographed on silica gel eluted with 0-10% methylene chloride in hexane. Recrystallization from methylene chloride hexane gave the title product as a white crystalline solid. mp 78-79° C.

Workup

  1. temperatureThis mixture was refluxed
  2. temperatureThe resulting mixture was then refluxed for 12 hours
  3. stirringwhile stirring under argon
  4. customThe solvent was removed in vacuo
  5. customthe residue was partitioned between ethyl acetate and water
  6. washThe organic phase was washed with water (2×), brine (1×)
  7. dry with materialdried over anhydrous Na2SO4
  8. filtrationfiltered
  9. customevaporated
  10. customto give the crude product which
  11. customwas then chromatographed on silica gel
  12. washeluted with 0-10% methylene chloride in hexane
  13. customRecrystallization from methylene chloride hexane

Sources & evidence

ORD record
ord-ddf4864685db4d2a8b495d0796807738
Source dataset
uspto-grants-2004_07
Patent number
US06759410B1

Reaction notes

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