Methyl iodide → 1,4-Dimethylindole

Temperature

0 °C

To a solution of 4-methyl-1H-indole (CAS#16096-32-5, 2.82 mL, 22.9 mmol) in THF (100 mL) at 0° C. was added sodium hydride (60% dispersion in oil, 1.37 g, 34.3 mmol). The reaction was permitted to stir for 16 minutes at 0° C. and was then warmed to room temperature for 60 minutes. The reaction mixture was then re-cooled to 0° C. and iodomethane (1.86 mL, 29.7 mmol) was added. The reaction was then put at room temperature and permitted to stir for 45 minutes. The reaction was then quenched with saturated aqueous ammonium chloride and concentrated to approximately half of its original volume. The mixture was then diluted with water and dichloromethane and the layers were separated. The aqueous layer was then extracted two additional times with dichloromethane. The organic layers were combined, dried over anhydrous sodium sulfate, filtered and concentrated. The resulting residue was purified by silica gel flash chromatography (ethyl acetate-heptane 0 to 30%) to afford 1,4-dimethyl-1H-indole; 1H NMR (400 MHz, CDCl3) δ ppm 2.57 (s, 3H), 3.80 (s 3H), 6.51 (d, J=3.0 Hz, 1H), 6.93 (d, J=6.7 Hz, 1H), 7.06 (d, J=3.0 Hz, 1H), 7.13-7.21 (m, 2H).

1. temperaturewas then warmed to room temperature for 60 minutes
2. temperatureThe reaction mixture was then re-cooled to 0° C.
3. customwas then put at room temperature
4. stirringto stir for 45 minutes
5. customThe reaction was then quenched with saturated aqueous ammonium chloride
6. concentrationconcentrated to approximately half of its original volume
7. additionThe mixture was then diluted with water and dichloromethane
8. customthe layers were separated
9. extractionThe aqueous layer was then extracted two additional times with dichloromethane
10. dry with materialdried over anhydrous sodium sulfate
11. filtrationfiltered
12. concentrationconcentrated
13. customThe resulting residue was purified by silica gel flash chromatography (ethyl acetate-heptane 0 to 30%)

ORD record

ord-e408a2f9ad844b78a3018476d3aa80cc

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08778972B2