Potassium Carbonate → 2-(3'-Chloro-3-fluorobiphenyl-4-yl)acetonitrile

HRID 70886Notes

Reaction equation

HRID 70886 reaction equation
Br[C:2]1[CH:10]=[CH:9][C:5]([CH2:6][C:7]#[N:8])=[C:4]([F:11])[CH:3]=1.[Cl:12][C:13]1[CH:14]=[C:15](B(O)O)[CH:16]=[CH:17][CH:18]=1.C([O-])([O-])=O.[K+].[K+]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.O.CCOC(C)=O.CC([O-])=O.CC([O-])=O.[Pd+2]>[Cl:12][C:13]1[CH:18]=[C:17]([C:2]2[CH:10]=[CH:9][C:5]([CH2:6][C:7]#[N:8])=[C:4]([F:11])[CH:3]=2)[CH:16]=[CH:15][CH:14]=1

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 2734323(3-Chlorophenyl)boronic acidHCID 71723082-(4-Bromo-2-fluorophenyl)acetonitrile

Product 1

HCID 596077962-(3'-Chloro-3-fluorobiphenyl-4-yl)acetonitrileYield 87.6%

Reagents, catalysts & solvents 4

HCID 74236Tetrabutylammonium BromideCatalystHCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

A suspension of 4-bromo-2-fluorobenzyl cyanide (3.50 g, 16.35 mmol), 3-chlorobenzeneboronic acid (2.68 g, 17.17 mmol), Pd(OAc)2 (0.110 g, 0.491 mmol), K2CO3 (5.65 g, 40.9 mmol) and tetrabutylammonium bromide (5.80 g, 17.99 mmol) in water (14 ml) is allowed to stir under nitrogen at 70° C. for 1 hour. The reaction mixture is cooled to room temperature, and diluted with EtOAc. The two phases are separated. The organic layer is washed with brine, dried over MgSO4, filtered and concentrated. The obtained residue is purified by silica gel flash column chromatography (heptane/EtOAc=100:0 to 70:30) to give 2-(3′-chloro-3-fluorobiphenyl-4-yl)acetonitrile (3.52 g); HPLC retention time=1.17 minutes (condition B); 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 3.81 (s, 2 H) 7.29-7.45 (m, 5 H) 7.50-7.55 (m, 2 H).

Workup

  1. temperatureThe reaction mixture is cooled to room temperature
  2. customThe two phases are separated
  3. washThe organic layer is washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe obtained residue is purified by silica gel flash column chromatography (heptane/EtOAc=100:0 to 70:30)

Sources & evidence

ORD record
ord-55e9ba74ea7a421b88130ab8228e81aa
Source dataset
uspto-grants-2014_09
Patent number
US08822534B2

Reaction notes

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