2-Bromobenzonitrile → 2'-Fluoro-5'-nitrobiphenyl-2-carbonitrile

HRID 586222Notes

Reaction equation

HRID 586222 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][C:3]=1B1OC(C)(C)C(C)(C)O1.Br[C:21]1[CH:28]=[CH:27][CH:26]=[CH:25][C:22]=1[C:23]#[N:24]>COCCOC.C([O-])(O)=O.[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>[F:1][C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][C:3]=1[C:21]1[C:22]([C:23]#[N:24])=[CH:25][CH:26]=[CH:27][CH:28]=1

Participants

6

Reactant 2

HCID 162722-BromobenzonitrileHCID 38332972-Fluoro-5-nitrophenylboronic acid, pinacol ester

Product 1

HCID 114478612'-Fluoro-5'-nitrobiphenyl-2-carbonitrileYield 43.4%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 2-(2-fluoro-5-nitrophenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (37.62 g, 0.141 mol), 2-bromobenzonitrile (35.30 g, 0.194 mol) and tetrakis(triphenylphosphine)palladium(0) (5.85 g, 5.06 mmol) in ethylene glycol dimethyl ether (350 ml) and saturated aqueous NaHCO3 (150 ml) was degassed by bubbling nitrogen through the mixture for 30 min. The mixture was then stirred at 90° C. under nitrogen for 15 h. After allowing to cool, the mixture was partitioned between dichloromethane (500 ml) and water (400 ml). The organic layer was washed with brine, dried (MgSO4), then passed through a pad of Florisil®, washing the product through with more dichloromethane. The filtrates were evaporated in vacuo, and the residue was triturated with diethyl ether (100 ml) and isohexane (100 ml). The resulting solid was collected by filtration, washed with 50% Et2O/isohexane and dried under vacuum to give 14.82 g (43%) of 2′-fluoro-5′-nitrobiphenyl-2-carbonitrile as a white solid. The combined filtrates were concentrated in vacuo to approximately 100 ml and the resulting solid was collected by filtration, washed with 20% Et2O/isohexane and dried under vacuum to give another 0.94 g (3%) of the product. The filtrates were evaporated in vacuo, and the residue was purified by flash chromatography (silica gel, 10-15% EtOAc/isohexane) to afford another 3.07 g (9%) of the product: 1H NMR (360 MHz, CDCl3) δ 7.40 (1H, t, J 8.5 Hz), 7.53 (1H, d, J 7.8 Hz), 7.59 (1H, td, J 7.7, 1.1 Hz), 7.74 (1H, td, J 7.7, 1.3 Hz), 7.84 (1H, dd, J 7.7, 0.9 Hz), 8.34-8.39 (2H, m).

Workup

  1. customwas degassed
  2. customby bubbling nitrogen through the mixture for 30 min
  3. temperatureto cool
  4. customthe mixture was partitioned between dichloromethane (500 ml) and water (400 ml)
  5. washThe organic layer was washed with brine
  6. dry with materialdried (MgSO4)
  7. washwashing the product through with more dichloromethane
  8. customThe filtrates were evaporated in vacuo
  9. customthe residue was triturated with diethyl ether (100 ml) and isohexane (100 ml)
  10. filtrationThe resulting solid was collected by filtration
  11. washwashed with 50% Et2O/isohexane
  12. customdried under vacuum

Sources & evidence

ORD record
ord-1383d1c70e4b4d979c92f9e6ec267934
Source dataset
uspto-grants-2005_08
Patent number
US06936608B2

Reaction notes

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