Methyl iodide → 4-Methoxy-1-methylindole

Temperature

0 °C

To a solution of 4-methoxy-1H-indole (CAS#4837-90-5, 4.0 g, 27.2 mmol) in THF (100 ml) at 0° C. was added sodium hydride (60% dispersion in oil, 1.63 g, 40.08 mmol). The reaction was stirred for 15 minutes at 0° C. and then put at room temperature for 1 h. The reaction was then re-cooled to 0° C. and iodomethane (2.209 ml, 35.3 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. Next, the reaction mixture was 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 4-methoxy-1-methyl-1H-indole; MS: (ES+) m/z 162.0 (M+H)+.

1. waitput at room temperature for 1 h
2. temperatureThe reaction 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. additionNext, the reaction mixture was 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-d1f78c374c5044569f7c89fa4d8614f4

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08778972B2