Tris(1,1-dimethylethyl)phosphine → 4,2'-Difluoro-5'-nitrobiphenyl-2-carbonitrile

HRID 2121371Notes

Reaction equation

HRID 2121371 reaction equation
Br[C:2]1[CH:9]=[CH:8][C:7]([F:10])=[CH:6][C:3]=1[C:4]#[N:5].[F:11][C:12]1[CH:17]=[CH:16][C:15]([N+:18]([O-:20])=[O:19])=[CH:14][C:13]=1B1OC(C)(C)C(C)(C)O1.[F-].[K+].C(P(C(C)(C)C)C(C)(C)C)(C)(C)C>O1CCCC1.O.O1CCOCC1.[OH-].[Na+].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:10][C:7]1[CH:6]=[C:3]([C:4]#[N:5])[C:2]([C:13]2[CH:14]=[C:15]([N+:18]([O-:20])=[O:19])[CH:16]=[CH:17][C:12]=2[F:11])=[CH:9][CH:8]=1

Participants

10

Reactant 4

HCID 83681Tris(1,1-dimethylethyl)phosphineHCID 936542-Bromo-5-fluorobenzonitrileHCID 522689Potassium FluorideHCID 38332972-Fluoro-5-nitrophenylboronic acid, pinacol ester

Product 1

HCID 112424114,2'-Difluoro-5'-nitrobiphenyl-2-carbonitrileYield 108%

Reagents, catalysts & solvents 5

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 14798Sodium HydroxideSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 2-bromo-5-fluorobenzonitrile (20 g, 100 mmol), 2-(2-fluoro-5-nitrophenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (from Example B) (34.7 g, 130 mmol) and potassium fluoride (19.2 g, 330 mmol) in tetrahydrofuran (350 ml) and water (20 ml) was degassed with nitrogen for 30 min then treated with tris(dibenzylideneacetone)dipalladium(0) (1.83 g, 2 mmol) followed by tri-tert-butylphosphine (4 ml of a 0.2 M solution in 1,4-dioxane, 0.8 mmol). This mixture was stirred at ambient temperature for 30 min before heating at 50° C. for 18 h. The resulting dark suspension was cooled to ambient temperature, diluted with 0.5 M sodium hydroxide (2.5 l) and stirred at ambient temperature for 4 h. The solid was collected by filtration, washed with water and dried under suction to afford 4,2′-difluoro-5′-nitrobiphenyl-2-carbonitrile as a black solid (28.1 g, >100%) contaminated with dibenzylideneacetone: 1H NMR (360 MHz, CDCl3) δ7.38-7.56 (4H, m), 8.33-8.40 (2H, m).

Workup

  1. customwas degassed with nitrogen for 30 min
  2. temperaturebefore heating at 50° C. for 18 h
  3. temperatureThe resulting dark suspension was cooled to ambient temperature
  4. stirringstirred at ambient temperature for 4 h
  5. filtrationThe solid was collected by filtration
  6. washwashed with water
  7. customdried under suction

Sources & evidence

ORD record
ord-5de95c5ad6384b8293f180443518dd48
Source dataset
uspto-grants-2004_02
Patent number
US06696444B2

Reaction notes

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