2-Chloronicotinonitrile → HCID 22285317, compound

HRID 586247Notes

Reaction equation

HRID 586247 reaction equation
Cl[C:2]1[N:9]=[CH:8][CH:7]=[CH:6][C:3]=1[C:4]#[N:5].[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.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[N:9]=[CH:8][CH:7]=[CH:6][C:3]=1[C:4]#[N:5]

Participants

8

Reactant 4

HCID 810792-ChloronicotinonitrileHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 522689Potassium FluorideHCID 38332972-Fluoro-5-nitrophenylboronic acid, pinacol ester

Product 1

HCID 22285317HCID 22285317, compoundYield 86%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
50 °C

Procedure

A mixture of 2-chloronicotinonitrile (2.49 g, 18.02 mmol), 2-(2-fluoro-5-nitrophenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (from Example 2, step d) (6.14 g, 23.43 mmol) and potassium fluoride (3.46 g, 59.47 mmol) in tetrahydrofuran (120 ml), was degassed with nitrogen for 30 min then treated with tris(dibenzylideneacetone)dipalladium(0) (0.33 g, 0.360 mmol), followed by tri-tert-butylphosphine (3.6 ml of a 0.2 M solution in 1,4-dioxane, 0.721 mmol). The mixture was degassed again before heating at 50° C. for 18 h. The mixture was cooled to ambient temperature then partitioned between ethyl acetate and water. The organic extracts were dried (Na2SO4), filtered and evaporated in vacuo. The residue was purified by flash chromatography (silica gel, CH2Cl2) to afford 3.759 g (86%) of the title compound: 1H NMR (360 MHz, CDCl3) δ 8.97 (1H, dd, J 5, 2 Hz), 8.56 (1H, dd, J 6, 3 Hz), 8.40-8.45 (1H, m), 8.15 (1H, dd, J 8, 2 Hz), 7.55 (1H, dd, J 8, 5 Hz), 7.43 (1H, dd, J 9, 9 Hz); MS (ES+) m/z 244 [M+H]+.

Workup

  1. customwas degassed with nitrogen for 30 min
  2. customThe mixture was degassed again
  3. temperatureThe mixture was cooled to ambient temperature
  4. customthen partitioned between ethyl acetate and water
  5. dry with materialThe organic extracts were dried (Na2SO4)
  6. filtrationfiltered
  7. customevaporated in vacuo
  8. customThe residue was purified by flash chromatography (silica gel, CH2Cl2)

Sources & evidence

ORD record
ord-9b504bd7d57e41d5a6746f9f8402872d
Source dataset
uspto-grants-2005_08
Patent number
US06936608B2

Reaction notes

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