Methyl iodide → 1-Methyl-1H-indole-6-carbonitrile

HRID 911336Notes

Reaction equation

HRID 911336 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:10]#[N:11])[CH:8]=2)[CH:3]=[CH:2]1.[H-].[Na+].I[CH3:15]>CN(C=O)C.[NH4+].[OH-]>[CH3:15][N:1]1[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:10]#[N:11])[CH:8]=2)[CH:3]=[CH:2]1

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 851461H-indole-6-carbonitrile

Product 1

HCID 153844931-Methyl-1H-indole-6-carbonitrileYield 604%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 14923Ammonium HydroxideSolvent

Procedure

Add slowly a solution of indole-6-carbonitrile (1.0 g, 7.04 mmol) in anhydrous DMF (5 mL) to a suspension of sodium hydride (60% dispersion in mineral oil, 0.6 g, 14.1 mmol) in anhydrous DMF (2 mL) at 0° C. and warm the reaction mixture to ambient temperature. Add iodomethane (0.7 mL, 1.06 mmol) and stir the reaction mixture for 1 h at ambient temperature. Dilute the reaction mixture with 1M aqueous NH4OH (30 mL) and extract with diethyl ether (3×10 mL). Combine the organic layers, dry over anhydrous Na2SO4, remove the solvent and purify by chromatography on silica gel eluting with hexane/EtOAc (1:0, 9:1, 4:1 and 7:3) to obtain the desired intermediate as a yellow oil (1.0 g, 87%). MS (ES+) m/z: 156 (M+H)+.

Workup

  1. extractionextract with diethyl ether (3×10 mL)
  2. dry with materialCombine the organic layers, dry over anhydrous Na2SO4
  3. customremove the solvent
  4. custompurify by chromatography on silica gel eluting with hexane/EtOAc (1:0, 9:1, 4:1 and 7:3)

Sources & evidence

ORD record
ord-4d52ffc3df464d578e4ebfba2c371fba
Source dataset
uspto-grants-2011_09
Patent number
US08022062B2

Reaction notes

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