N,N'-Dimethylethylenediamine → Indole-5-carbonitrile

HRID 2180659Notes

Reaction equation

HRID 2180659 reaction equation
[C-]#N.[Na+].Br[C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[NH:10][CH:9]=[CH:8]2.[CH3:14][NH:15]CCNC.[OH-].[NH4+]>[Cu]I.O.C(OCC)(=O)C.C1(C)C=CC=CC=1>[NH:10]1[C:11]2[C:7](=[CH:6][C:5]([C:14]#[N:15])=[CH:13][CH:12]=2)[CH:8]=[CH:9]1

Participants

9

Reactant 4

HCID 8070N,N'-DimethylethylenediamineHCID 8929Sodium CyanideHCID 14923Ammonium HydroxideHCID 249055-Bromoindole

Product 1

HCID 27513Indole-5-carbonitrileYield 95%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

An oven dried screw cap test tube was charged with NaCN (98 mg, 2.00 mmol) dried KI (55 mg, 0.331 mmol, 20 mol %) and CuI (32 mg, 0.168 mmol, 10 mol %), 5-Bromoindole (327 mg, 1.667 mmol), evacuated and backfilled with argon three times. Anhydrous toluene (1.1 mL) and N,N′-dimethylethylenediamine (180 μL, 1.691 mmol) were added under argon. The tube was sealed and the reaction mixture was stirred magnetically at 110° C. for 24 h. The resulting yellow color suspension was cooled to room temperature, 2 mL of ethyl acetate, 1 mL of ammonium hydroxide 30% and 1 mL of water were added. The mixture was stirred at 25° C. for 10 min then the organic layer was separated and the aqueous layer was extracted three times with ethyl acetate (3×2 mL). The organic layers combined were washed with 5 mL of water and dried over MgSO4. The GC analysis showed complete conversion of starting material with a desired product area of 99%. The solvent was removed at reduced pressure. Purification of the residue by flash chromatography on silica gel (2×15 cm; hexane/ethyl acetate 10:1) provided 225 mg (95% yield) of the title compound as a white solid.

Workup

  1. customAn oven dried screw
  2. customcap test tube
  3. customevacuated
  4. customThe tube was sealed
  5. temperatureThe resulting yellow color suspension was cooled to room temperature
  6. stirringThe mixture was stirred at 25° C. for 10 min
  7. customthe organic layer was separated
  8. extractionthe aqueous layer was extracted three times with ethyl acetate (3×2 mL)
  9. washThe organic layers combined were washed with 5 mL of water
  10. dry with materialdried over MgSO4
  11. customThe solvent was removed at reduced pressure
  12. customPurification of the residue by flash chromatography on silica gel (2×15 cm; hexane/ethyl acetate 10:1)

Sources & evidence

ORD record
ord-f1df890943ab476cae21bf2d0c87e42c
Source dataset
uspto-grants-2005_05
Patent number
US06888032B2

Reaction notes

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