Toluene → 2'-Fluoro-4'-(hydroxymethyl)biphenyl-2-carbonitrile

HRID 2048280Notes

Reaction equation

HRID 2048280 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([CH:8]=[O:9])[CH:5]=[CH:4][C:3]=1B(O)O.[C:13]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1B(O)O)#[N:14].C(=O)([O-])[O-].[Na+].[Na+].C1(C)C=CC=CC=1>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C(OCC)(=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:1][C:2]1[CH:7]=[C:6]([CH2:8][OH:9])[CH:5]=[CH:4][C:3]=1[C:16]1[C:15]([C:13]#[N:14])=[CH:20][CH:19]=[CH:18][CH:17]=1

Participants

8

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 27346102-Cyanophenylboronic acidHCID 162180452-Fluoro-4-formylbenzeneboronic acid

Product 1

HCID 670099902'-Fluoro-4'-(hydroxymethyl)biphenyl-2-carbonitrileYield 30%

Reagents, catalysts & solvents 3

HCID 74236Tetrabutylammonium BromideCatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of (2-fluoro-4-formylphenyl)boronic acid (35.3 g), 2-cyano-phenylboronic acid (40.0 g), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium (1.7 g), tetrabutylammonium bromide (0.68 g), 2M aqueous sodium carbonate solution (200 mL) and toluene (600 mL) was stirred at 100° C. for 72 hr under an argon atmosphere. The reaction mixture was diluted with ethyl acetate, washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was dissolved in tetrahydrofuran (150 mL) and methanol (150 mL), sodium borohydride (8.7 g) was added, and the mixture was stirred at room temperature for 1 hr. After evaporation of the solvent under reduced pressure, the residue was extracted with water and ethyl acetate. The obtained ethyl acetate layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography to give the title compound as a colorless solid (14.1 g, 30%).

Workup

  1. washwashed with saturated brine
  2. dry with materialdried over anhydrous magnesium sulfate
  3. customThe solvent was evaporated under reduced pressure
  4. dissolutionThe obtained residue was dissolved in tetrahydrofuran (150 mL)
  5. additionmethanol (150 mL), sodium borohydride (8.7 g) was added
  6. stirringthe mixture was stirred at room temperature for 1 hr
  7. customAfter evaporation of the solvent under reduced pressure
  8. extractionthe residue was extracted with water and ethyl acetate
  9. washThe obtained ethyl acetate layer was washed with saturated brine
  10. dry with materialdried over anhydrous magnesium sulfate
  11. customThe solvent was evaporated under reduced pressure
  12. customthe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-a50806834e504c8dbf44edac6a37e017
Source dataset
uspto-grants-2013_11
Patent number
US08592431B2

Reaction notes

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