Hydrochloric Acid → 6-Bromo-1-methyl-1H-indole

HRID 1791410Notes

Reaction equation

HRID 1791410 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].Cl>C1COCC1.O>[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

7

Reactant 4

HCID 313Hydrochloric AcidHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 6764936-Bromoindole

Product 1

HCID 155468546-Bromo-1-methyl-1H-indoleYield 81.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 6-bromo-1H-indole (2.34 g, 11.9 mmol) in dry THF (25 mL) was cooled in an ice bath. Sodium hydride (1.12 g of 60% dispersion in oil, 28.0 mmol) was added. The mixture was stirred for 30 minutes under nitrogen at room temperature, then cooled in an ice bath. Iodomethane (1.6 mL, 26 mmol) was added. The reaction mixture was stirred for 2 hours at room temperature, poured into excess water, acidified with 2N hydrochloric acid and extracted with ethyl acetate. The organic phase was washed with water and brine, dried over anhydrous magnesium sulfate and evaporated to dryness. The residue was purified by flash chromatography using hexane as an eluant to yield 6-bromo-1-methyl-1H-indole 2.04 g (81.6%, 9.71 mmol) as a yellow oil. 1HNMR (200 MHz, DMSO-d6): δ 7.7 (s, 1H), 7.5 (d, 1H, J=8.6 Hz), 7.35 (d, 1H, J=2.1 Hz), 7.15 (d, 1H, 7.3 Hz), 6.4 (d, 1H, J=1.3 Hz), and 3.75 ppm (s, 3H).

Workup

  1. temperaturecooled in an ice bath
  2. stirringThe reaction mixture was stirred for 2 hours at room temperature
  3. extractionextracted with ethyl acetate
  4. washThe organic phase was washed with water and brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customevaporated to dryness
  7. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-0383f094cf274dcb95ace383024d4ee3
Source dataset
uspto-grants-2006_07
Patent number
US07074817B2

Reaction notes

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