Tris(1,1-dimethylethyl)phosphine → 4-(2-Fluoro-5-nitrophenyl)nicotinonitrile

HRID 586281Notes

Reaction equation

HRID 586281 reaction equation
Br[C:2]1[C:7]([C:8]#[N:9])=[CH:6][N:5]=[CH:4][CH:3]=1.[F:10][C:11]1[CH:16]=[CH:15][C:14]([N+:17]([O-:19])=[O:18])=[CH:13][C:12]=1B1OC(C)(C)C(C)(C)O1.[F-].[K+].C(P(C(C)(C)C)C(C)(C)C)(C)(C)C>O1CCCC1.O1CCOCC1.O.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:11]1[CH:16]=[CH:15][C:14]([N+:17]([O-:19])=[O:18])=[CH:13][C:12]=1[C:2]1[C:7]([C:8]#[N:9])=[CH:6][N:5]=[CH:4][CH:3]=1

Participants

9

Reactant 4

HCID 83681Tris(1,1-dimethylethyl)phosphineHCID 522689Potassium FluorideHCID 38332972-Fluoro-5-nitrophenylboronic acid, pinacol esterHCID 223295224-Bromopyridine-3-carbonitrile

Product 1

HCID 223295054-(2-Fluoro-5-nitrophenyl)nicotinonitrile

Reagents, catalysts & solvents 4

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

Procedure

A mixture of 4-bromonicotinonitrile (1.00 g, 5.46 mmol), 2-(2-fluoro-5-nitrophenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (1.90 g, 7.10 mmol) and potassium fluoride (1.05 g, 18.03-mmol) in tetrahydrofuran (50 ml) was degassed with nitrogen for 30 min then treated with tris(dibenzylideneacetone)dipalladium(0) (0.05 g, 0.05 mmol) followed by tri-tert-butylphosphine (0.60 ml of a 0.2 M solution in 1,4-dioxane, 0.11 mmol) and then the reaction was stirred at ambient temperature for 30 min before heating at 50° C. for 1 h to complete the coupling. The slurry-like reaction mixture was then diluted with water (100 ml) and stirred at ambient temperature for 90 min. The resulting solid was collected by filtration, washed with water then with isohexane, and finally dried under vacuum over phosphorus pentoxide, to afford 4-(2-fluoro-5-nitrophenyl)-nicotinonitrile as a white solid: 1H NMR (400 MHz, CDCl3) δ 7.44-7.52 (2H, m), 8.38-8.47 (2H, m), 8.95 (1H, d, J 5 Hz), 9.06 (1H, s).

Workup

  1. customwas degassed with nitrogen for 30 min
  2. temperaturebefore heating at 50° C. for 1 h
  3. customThe slurry-like reaction mixture
  4. stirringstirred at ambient temperature for 90 min
  5. filtrationThe resulting solid was collected by filtration
  6. washwashed with water
  7. dry with materialwith isohexane, and finally dried under vacuum over phosphorus pentoxide

Sources & evidence

ORD record
ord-8b1f45702a7c47658f2380cc90e6d24b
Source dataset
uspto-grants-2005_08
Patent number
US06936608B2

Reaction notes

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