Methyl iodide → 1,3-Dimethylindole

HRID 1921013Notes

Reaction equation

HRID 1921013 reaction equation
[CH3:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[NH:4][CH:3]=1.[H-].[Na+].I[CH3:14]>CN(C=O)C>[CH3:14][N:4]1[C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[C:2]([CH3:1])=[CH:3]1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 6736SkatoleHCID 24758Sodium hydride

Product 1

HCID 701301,3-DimethylindoleYield 97.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 3-methylindole (15.0 g, 114 mmole) in dry DMF (200 mL) was added NaH (60% dispersion in oil, 5.0 g, 125 mmole) in portions. Gas evolution was observed. The mixture was stirred for 30 min, then iodomethane (8 mL, 129 mmole) was added in one portion. The reaction became exothermic and was cooled in an ice bath. After 16 hr at RT, the reaction was concentrated under vacuum and the residue was taken up in ethyl acetate. The solution was washed with H2O then with brine, dried (MgSO4), and concentrated to dryness. Purification by short path distillation under vacuum (bp 88-92° C., 05 mmHg) gave the title compound (16.10 g, 97%) as a pale yellow oil: 1H NMR (400 MHz, CDCl3) δ 7.47 (d, J=7.9 Hz, 1H), 7.35 (d, J=8.2 Hz, 1H), 7.13 (t, 1H), 7.06 (s, 1H), 7.00 (t, 1H), 3.71 (s, 3H), 2.24 (s, 3H).

Workup

  1. temperaturewas cooled in an ice bath
  2. waitAfter 16 hr at RT
  3. concentrationthe reaction was concentrated under vacuum
  4. washThe solution was washed with H2O
  5. dry with materialwith brine, dried (MgSO4)
  6. concentrationconcentrated to dryness
  7. customPurification
  8. distillationby short path distillation under vacuum (bp 88-92° C., 05 mmHg)

Sources & evidence

ORD record
ord-316a75f44e094fccac6a7f485ded810e
Source dataset
uspto-grants-2012_05
Patent number
US08173646B2

Reaction notes

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