Methyl iodide → 4-Bromo-1,5-dimethyl-1H-indole

HRID 857941Notes

Reaction equation

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

Participants

Conditions

Temperature: 0 °C

Procedure

A solution of 4-bromo-5-methylindole (3.55 g, 16.9 mmol) (21) in 10 ml of anhydrous DMF is added to a suspension of sodium hydride (1.01 g, 60% in mineral oil, 25.3 mmol, 1.5 eq.) in 10 ml of DMF under nitrogen at 0° C. The resulting mixture is stirred at 0° C. for 30 minutes, and then warmed to room temperature. After stirring at room temperature for an additional 2 hours, the reaction mixture is cooled to 0° C. Iodomethane (2.40 g, 18.6 mmol, 1.1 eq.) is added dropwise, the mixture is stirred at 0° C. for 2 hours, and then is warmed to 50° C. and stirred for an additional 2 hours. The reaction mixture is poured into 100 ml of ice-water, extracted with ethyl acetate (30 ml×3), washed with water and brine dried over anhydrous sodium sulfate. The solvent is evaporated and the product (22) is taken to dryness under high vacuum to give 3.75 g of pure compound. 1H NMR (400 MHz, CDCl3) δ 7.17 (1H, d, J=8.4 Hz), 7.08 (1H, d, J=8.4 Hz), 7.05 (1H, 4, J=3.2 Hz), 650 (1H, dd, J=0.4, 2.8 Hz), 3.77 (3H, 3), 2.51 (3H, s); MS (+VE) m/z 224 (M+).

Workup

temperaturewarmed to room temperature
stirringAfter stirring at room temperature for an additional 2 hours
temperaturethe reaction mixture is cooled to 0° C
stirringthe mixture is stirred at 0° C. for 2 hours
temperatureis warmed to 50° C.
stirringstirred for an additional 2 hours
extractionextracted with ethyl acetate (30 ml×3)
washwashed with water and brine
dry with materialdried over anhydrous sodium sulfate
customThe solvent is evaporated

Sources & evidence

ORD record: ord-43eff373400c47d19e9978021eb2c9e5
Source dataset: uspto-grants-2006_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07148225B2

Reaction notes

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