Methyl iodide → 1,4,6-Trimethyl-1H-indole

HRID 388471Notes

Reaction equation

HRID 388471 reaction equation
[CH3:1][C:2]1[CH:10]=[C:9]([CH3:11])[CH:8]=[C:7]2[C:3]=1[CH:4]=[CH:5][NH:6]2.[H-].[Na+].I[CH3:15]>CN(C=O)C>[CH3:15][N:6]1[C:7]2[C:3](=[C:2]([CH3:1])[CH:10]=[C:9]([CH3:11])[CH:8]=2)[CH:4]=[CH:5]1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 98339914,6-dimethyl-1H-indole

Product 1

HCID 134110531,4,6-Trimethyl-1H-indoleYield 84.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of the 4,6-dimethylindole (750 mg, 5.2 mmol) in DMF (20 mL) is cooled to 0° C. under nitrogen and is treated with 60% sodium hydride in mineral oil (413 mg, 10.3 mmol). After stirring for 15 minutes the iodomethane (0.4 mL, 6.2 mmol) is introduced and the cooling bath is removed. After 30 minutes the solution is quenched with water (5 ml) and then concentrates to reduce the volume of DMF. The reaction is poured into a mixture of water (200 mL) and EtOAc (100 mL). The layers are separated and the aqueous phase is extracted with EtOAc (3×200 mL). The combined organics are washed with water (3×), dried (MgSO4), filtered and concentrated. The residue is purified by flash chromatography with 10% EtOAc in Hexane as the eluent to afford 1,4,6-Trimethyl-1H-indole (700 mg, 80%) as a white solid.

Workup

  1. additionis introduced
  2. customthe cooling bath is removed
  3. customAfter 30 minutes the solution is quenched with water (5 ml)
  4. additionThe reaction is poured into a mixture of water (200 mL) and EtOAc (100 mL)
  5. customThe layers are separated
  6. extractionthe aqueous phase is extracted with EtOAc (3×200 mL)
  7. washThe combined organics are washed with water (3×)
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe residue is purified by flash chromatography with 10% EtOAc in Hexane as the eluent

Sources & evidence

ORD record
ord-721b06de16664ba9818dd8c6575ac969
Source dataset
uspto-grants-2013_02
Patent number
US08377949B2

Reaction notes

Loading…