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

HRID 1167120Notes

Reaction equation

HRID 1167120 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) δ 7.38-7.56 (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-e297d0692ae94dd882d2b5ef5e2c80f7
Source dataset
uspto-grants-2003_09
Patent number
US06617326B2

Reaction notes

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