Water → 4-[4-(Pyridin-2-yl)but-3-yn-1-yl]benzonitrile

HRID 982693Notes

Reaction equation

HRID 982693 reaction equation
[CH2:1]([C:5]1[CH:12]=[CH:11][C:8]([C:9]#[N:10])=[CH:7][CH:6]=1)[CH2:2][C:3]#[CH:4].C(N(CC)CC)C.Br[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=1.O>C1COCC1.[Pd].[Cu]I.C(OCC)(=O)C>[N:22]1[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=1[C:4]#[C:3][CH2:2][CH2:1][C:5]1[CH:6]=[CH:7][C:8]([C:9]#[N:10])=[CH:11][CH:12]=1

Participants

9

Reactant 4

HCID 962WaterHCID 79732-BromopyridineHCID 8471TriethylamineHCID 225632104-(But-3-yn-1-yl)benzonitrile

Product 1

HCID 225632064-[4-(Pyridin-2-yl)but-3-yn-1-yl]benzonitrileYield 79.6%

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
65 °C

Procedure

A dried 1 L of three-neck round-bottom flask was flushed with N2, connected to a N2 inlet, equipped with a thermometer and a magnetic stirrer. 4-But-3-ynyl-benzonitrile (49.38 g, 0.32 mol) was dissolved in 250 mL of THF, followed by the successive addition of triethylamine (TEA) (250 mL, 1:1 TEA/THF), bromopyridine (33.3 mL, 0.35 mol), Pd (pph3)2Cl2 (4.47 g, 6.0 mmol), and CuI (1.21 g, 6.0 mmol). The reaction mixture was heated up to 65° C. and kept stirring at that temperature. During the heating, it turned dark brown. After 2 h, the reaction was complete and cooled to room temperature, followed by the addition of water (200 mL) and ethyl acetate (200 mL). The organic layer was separated, washed with water (30 mL) and brine (30 mL), and dried over sodium sulfate. After a simple filtration to remove any catalyst residues and drying agents, concentration in vacuo left an oil, which immediately became solid after cooling. The solid was then filtered and washed with heptane to give 58.74 g (79.6% yield; purity: 98%) of 4-(4-pyridin-2-yl-but-3-ynyl)-benzonitrile. 1H NMR (CDCl3): δ (ppm) 8.54 (m, 1H); 7.59 (m, 3H); 7.39 (m, 2H); 7.31 (m, 1H); 7.19 (m, 1H); 3.01 (t, J=6.9 Hz, 2H); 2.75 (t, J=6.9 Hz, 2H). ESMS calcd. (C16H12N2): 232.1. found: 233.1 (M+H)+.

Workup

  1. customA dried 1 L of three-neck round-bottom flask was flushed with N2
  2. customconnected to a N2 inlet
  3. customequipped with a thermometer and a magnetic stirrer
  4. temperaturecooled to room temperature
  5. customThe organic layer was separated
  6. washwashed with water (30 mL) and brine (30 mL)
  7. dry with materialdried over sodium sulfate
  8. filtrationAfter a simple filtration
  9. customto remove any catalyst residues
  10. customdrying
  11. concentrationagents, concentration in vacuo
  12. waitleft an oil, which immediately became solid
  13. temperatureafter cooling
  14. filtrationThe solid was then filtered
  15. washwashed with heptane

Sources & evidence

ORD record
ord-d94a8e85d838447cab62c309d8e6c515
Source dataset
uspto-grants-2005_03
Patent number
US06861436B2

Reaction notes

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