Dimethylacetamide → 4-[(Indolizin-3-yl)methyl]benzonitrile

HRID 982694Notes

Reaction equation

HRID 982694 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]#[C:8][CH2:9][CH2:10][C:11]1[CH:18]=[CH:17][C:14]([C:15]#[N:16])=[CH:13][CH:12]=1.CC(N(C)C)=O>C(OCC)(=O)C.Cl[Cu]>[CH:7]1[CH:8]=[C:9]([CH2:10][C:11]2[CH:12]=[CH:13][C:14]([C:15]#[N:16])=[CH:17][CH:18]=2)[N:1]2[C:2]=1[CH:3]=[CH:4][CH:5]=[CH:6]2

Participants

5

Reactant 2

HCID 31374DimethylacetamideHCID 225632064-[4-(Pyridin-2-yl)but-3-yn-1-yl]benzonitrile

Product 1

HCID 225632004-[(Indolizin-3-yl)methyl]benzonitrileYield 92.8%

Reagents, catalysts & solvents 2

HCID 62652Cuprous chlorideCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
130 °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-(4-Pyridin-2-yl-but-3-ynyl)-benzonitrile (58.73 g, 0.25 mol), DMA (490 mL) and TEA (70 mL) were successively added to the flask, resulting in a light brown solution. CuCl (25.05 g, 0.25 mol) was then added, after which the reaction turned dark brown. The reaction mixture was kept stirring at 130° C. After stirring for 3 h at 130° C., the reaction was complete, and cooled to room temperature. The reaction was then quenched with water (300 mL), and ethyl acetate (400 mL) was added. The resulting dark brown mixture was then filtered through a celite cake to give a clear two-layer mixture. After separation, drying, and concentration, a dark oil was obtained. The dark oil was dissolved in 250 mL of ethyl acetate, applied to 15 g of decoloring carbon, and stirred for 20 minutes. After filtration through a celite cake, the filtrate was washed with water (100 mL) twice, dried over sodium sulfate. Concentration gave 53.89 g (89%) of 4-indolizin-3-ylmethyl-benzonitrile. 1H NMR (CDCl3): δ (ppm) 7.55 (d, J=8.1 Hz, 2H); 7.50 (d, J=9.0 Hz, 1H); 7.39 (d, J=9.0 Hz, 1H); 7.23 (d, J=7.8 Hz, 2H); 6.64 (m, 2H), 6.44 (m, 2H); 4.27 (s, 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. customresulting in a light brown solution
  5. stirringAfter stirring for 3 h at 130° C.
  6. temperaturecooled to room temperature
  7. customThe reaction was then quenched with water (300 mL), and ethyl acetate (400 mL)
  8. additionwas added
  9. filtrationThe resulting dark brown mixture was then filtered through a celite cake
  10. customto give a clear two-layer mixture
  11. customAfter separation
  12. customdrying
  13. concentrationconcentration
  14. customa dark oil was obtained
  15. stirringstirred for 20 minutes
  16. filtrationAfter filtration through a celite cake
  17. washthe filtrate was washed with water (100 mL) twice
  18. dry with materialdried over sodium sulfate
  19. concentrationConcentration

Sources & evidence

ORD record
ord-8976d172c1f747c1acae97b7ad0ae38a
Source dataset
uspto-grants-2005_03
Patent number
US06861436B2

Reaction notes

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