Methyl iodide → 6-Bromo-1-methyl-1H-indole

HRID 1524383Notes

Reaction equation

HRID 1524383 reaction equation
[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[CH:7][NH:8]2)=[CH:4][CH:3]=1.[H-].[Na+].I[CH3:14]>C1COCC1>[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[CH:7][N:8]2[CH3:14])=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 6764936-Bromoindole

Product 1

HCID 155468546-Bromo-1-methyl-1H-indoleYield 91%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A 1-round-bottom flask was charged with 6-bromo-1H-indole (14.88 g, 76 mmol) and THF (150 ml) to give a dark maroon solution. The flask was put under a N2 sweep, and sodium hydride (60 wt %) (3.64 g, 91 mmol) was added in several portions over 15 min. The resulting mixture was stirred for 20 min, then iodomethane (5.94 ml, 95 mmol) was added via syringe. Within a few minutes, an exotherm was observed. After stirring for 20 min, the mixture was concentrated in vacuo, and the residue was taken up in saturated aq. sodium bicarbonate solution and extracted with DCM (3×). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated. The crude product was purified by chromatography on silica gel (0 to 40% EtOAc/Heptane) to afford 6-bromo-1-methyl-1H-indole (14.44 g, 68.7 mmol, 91% yield) as a lightly colored oil. 1H NMR (400 MHz, CDCl3) δ=7.51-7.46 (m, 2 H), 7.24-7.19 (m, 1 H), 7.03 (d, J=3.1 Hz, 1 H), 6.47 (dd, J=0.9, 3.1 Hz, 1 H), 3.77 (s, 3 H).

Workup

  1. customto give a dark maroon solution
  2. additionwas added in several portions over 15 min
  3. waitWithin a few minutes
  4. stirringAfter stirring for 20 min
  5. concentrationthe mixture was concentrated in vacuo
  6. extractionextracted with DCM (3×)
  7. dry with materialThe combined organic extracts were dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude product was purified by chromatography on silica gel (0 to 40% EtOAc/Heptane)

Sources & evidence

ORD record
ord-a94b5c3f827f43f7a81f95a6efc2da90
Source dataset
uspto-grants-2015_07
Patent number
US09079902B2

Reaction notes

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