Potassium Fluoride → 3,2'-Difluoro-5'-nitrobiphenyl-2-carbonitrile

HRID 2183960Notes

Reaction equation

HRID 2183960 reaction equation
Br[C:2]1[CH:9]=[CH:8][CH:7]=[C:6]([F:10])[C:3]=1[C:4]#[N:5].[F-].[K+].[F:13][C:14]1[CH:19]=[CH:18][C:17]([N+:20]([O-:22])=[O:21])=[CH:16][C:15]=1B1OC(C)(C)C(C)(C)O1>O1CCCC1>[F:10][C:6]1[CH:7]=[CH:8][CH:9]=[C:2]([C:15]2[CH:16]=[C:17]([N+:20]([O-:22])=[O:21])[CH:18]=[CH:19][C:14]=2[F:13])[C:3]=1[C:4]#[N:5]

Participants

5

Reactant 3

HCID 522689Potassium FluorideHCID 27831392-Bromo-6-fluorobenzonitrileHCID 38332972-Fluoro-5-nitrophenylboronic acid, pinacol ester

Product 1

HCID 222852823,2'-Difluoro-5'-nitrobiphenyl-2-carbonitrileYield 100%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A suspension of 2-bromo-6-fluorobenzonitrile (2.50 g, 12.5 mmol), potassium fluoride (2.40 g, 41.3 mmol) and 2-(2-fluoro-5-nitrophenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (4.67 g, 17.5 mmol) in tetrahydrofuran (50 ml) was degassed with nitrogen for 30 min. Tris(dibenzylideneacetone)dipalladium(0) and tri-tert-butylphosphine (0.2M solution in 1,4-dioxane, 3.7 ml) were added and the mixture stirred at ambient temperature for 15 min then at 50° C. for 18 h. After cooling to ambient temperature, the resulting dark suspension was poured onto 0.5M sodium hydroxide solution (500 ml) and stirred vigorously for 2 h. The dark solid was collected by filtration, washed with water (100 ml) and isohexane (50 ml) and left to air dry which gave 3,2′-difluoro-5′-nitrobiphenyl-2-carbonitrile as a brown/black solid (3.25 g, 100%): δH (360 MHz, CDCl3) 7.32-7.44 (3H, m), 7.71-7.77 (1H, m), 8.35-8.41 (2H, m). 3,2′-Difluoro-5′-nitrobiphenyl-2-carbonitrile (3.25 g, 12.5 mmol) in tetrahydrofuran (20 ml) and ethanol (20 ml) was treated with tin(II) chloride dihydrate (9.86 g, 43.8 mmol) and the mixture left to stir at ambient temperature for 18 h. The solvent was evaporated and the residue stirred with 2N sodium hydroxide solution (40 ml) for 2 h. The resulting suspension was diluted with water (100 ml) and extracted with dichloromethane (3×200 ml). The combined organics were washed with water (200 ml), brine (200 ml), dried over anhydrous sodium sulfate, filtered and evaporated to give 5′-amino-3,2′-difluorobiphenyl-2-carbonitrile as a brown solid (2.87 g, 100%): δH (360 MHz, CDCl3) 3.74 (2H, s), 6.66-6.75 (2H, m), 7.01 (1H, dd, J 9 and 9), 7.19-7.30 (2H, m), 7.59-7.65 (1H, m).

Workup

  1. customwas degassed with nitrogen for 30 min
  2. additionTris(dibenzylideneacetone)dipalladium(0) and tri-tert-butylphosphine (0.2M solution in 1,4-dioxane, 3.7 ml) were added
  3. waitat 50° C. for 18 h
  4. temperatureAfter cooling to ambient temperature
  5. additionthe resulting dark suspension was poured onto 0.5M sodium hydroxide solution (500 ml)
  6. stirringstirred vigorously for 2 h
  7. filtrationThe dark solid was collected by filtration
  8. washwashed with water (100 ml) and isohexane (50 ml)
  9. waitleft to air
  10. customdry which

Sources & evidence

ORD record
ord-2582a8e701904ebabe249e76539b23d7
Source dataset
uspto-grants-2005_05
Patent number
US06900215B2

Reaction notes

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