Hydrochloric Acid → 1-Benzyl-5-Bromo-1H-Indole

HRID 1373344Notes

Reaction equation

HRID 1373344 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[CH:5]2.[H-].[Na+].[CH2:13](Br)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.Cl>CN(C=O)C.O>[CH2:13]([N:7]1[C:8]2[C:4](=[CH:3][C:2]([Br:1])=[CH:10][CH:9]=2)[CH:5]=[CH:6]1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 249055-Bromoindole

Product 1

HCID 2857561-Benzyl-5-Bromo-1H-IndoleYield 78%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of 5-bromoindole (5.02 g, 25.6 mmol) in DMF (50 mL) was cooled in an ice bath. Sodium hydride (2.30 g of 60% dispersion in oil, 57.5 mmol) was added. After stirring for 40 minutes under nitrogen at room temperature, the reaction mixture was again cooled in an ice bath and benzyl bromide (6.7 mL, 56 mmol) was added. The reaction mixture was stirred for 2 hours, 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 (Biotage apparatus) using hexane as an eluant. Dyring at 60° C. for 35 minutes yielded the title compound as a white solid (5.69 g, 78%), mp 93–95° C. Mass spectrum (+ESI, [M+H]+) m/z 286; 1HNMR (500 MHz, DMSO-d6): δ7.7 (d, 1H, J=1.8 Hz), 7.55 (d, 1H, J=3.1 Hz), 7.4 (d, 1H, J=8.7 Hz), 7.15–7.30 (m, 6H), 6.45 (dd, 1H, J=3.2 Hz and 0.6 Hz), and 5.45 ppm (s, 2H).

Workup

  1. temperaturethe reaction mixture was again cooled in an ice bath
  2. stirringThe reaction mixture was stirred for 2 hours
  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 (Biotage apparatus)
  8. waitDyring at 60° C. for 35 minutes

Sources & evidence

ORD record
ord-cbbe27a5cd4849c98fddc01d401adfd9
Source dataset
uspto-grants-2007_01
Patent number
US07160918B2

Reaction notes

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