Sodium Cyanide → Indole-5-carbonitrile

HRID 710293

Reaction equation

HRID 710293 reaction equation
I[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[CH:5]2.[C-:11]#[N:12].[Na+]>CC#N.CCOC(C)=O.[Cu]I>[C:11]([C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[CH:5]2)#[N:12]

Participants

6

Reactant 2

HCID 8929Sodium CyanideHCID 27823135-Iodo-1H-indole

Product 1

HCID 27513Indole-5-carbonitrileYield 95.1%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 5-iodoindole (0.36 g; 1.48 mmol), NaCN (0.15 g; 3 mmol), Pd(Ph3)4 (0.23 g; 0.22 mmol) and CuI (0.06 g; 0.3 mmol) in anhydrous CH3CN (3 ml) was refluxed for 2.5 h under N2. After cooling to room temperature, the mixture was diluted to 20 ml with EtOAc and filtered through a pad of Celite. The filtrate was washed with H2O, brine, dried over anhydrous MgSO4 and filtered. The filtrate was evaporated to dryness under reduced pressure, dissolved in a small volume of CH2Cl2 and filtered through a small pad of SiO2, which was washed with fresh CH2Cl2. The combined filtrates were evaporated to dryness under reduced pressure to give the title compound (0.2 g; 95%) as colourless solid. 1H-NMR (CDCl3) 6.62 (tr, 1H, J=2.5 Hz); 7.33 (tr, 1H, J=2.5 Hz); 7.39-7.47 (m, 2H); 7.98 (s, 1H); 8.51 (broad s, 1H).

Workup

  1. temperaturewas refluxed for 2.5 h under N2
  2. filtrationfiltered through a pad of Celite
  3. washThe filtrate was washed with H2O, brine
  4. dry with materialdried over anhydrous MgSO4
  5. filtrationfiltered
  6. customThe filtrate was evaporated to dryness under reduced pressure
  7. dissolutiondissolved in a small volume of CH2Cl2
  8. filtrationfiltered through a small pad of SiO2, which
  9. washwas washed with fresh CH2Cl2
  10. customThe combined filtrates were evaporated to dryness under reduced pressure

Sources & evidence

ORD record
ord-06aff8e3d2e940f5acd987d69ad40d19
Source dataset
uspto-grants-2015_11
Patent number
US09181182B2

Linked notes

Loading…