Indole → 1-Methylindole

Temperature

130 °C

Indole (10 g, 85.4 mmole), potassium carbonate (5 g), N,N-dimethylformamide (70 mL) and dimethyl carbonate (11 mL, 0.13 mol) were mixed together and refluxed (˜130° C.) for 2 h. At this point TLC analysis of the reaction showed two compounds, the N-methylated indole along with a significant amount of starting material. The reaction mixture was cooled down to ˜50° C. and a second portion of dimethyl carbonate (5.5 mL, 0.065 mol) was added. The mixture was heated at reflux for another 7 h until TLC analysis indicated total consumption of starting indole. The reaction mixture was cooled down to room temperature and it was slowly diluted with water (150 mL). The resulting mixture was extracted with tert-butyl methyl ether (150 mL) and the separated organic layer was washed with water (2×100 mL). The solvent was evaporated in vacuao to furnish 10.8 g of 1-methylindole as light yellow oil (96.5% yield).

1. temperatureThe reaction mixture was cooled down to ˜50° C.
2. temperatureThe mixture was heated
3. temperatureat reflux for another 7 h until TLC analysis
4. customconsumption of starting indole
5. temperatureThe reaction mixture was cooled down to room temperature
6. additionit was slowly diluted with water (150 mL)
7. extractionThe resulting mixture was extracted with tert-butyl methyl ether (150 mL)
8. washthe separated organic layer was washed with water (2×100 mL)
9. customThe solvent was evaporated in vacuao

ORD record

ord-477fee09e67c4c61b55fdd2c8043059b

Source dataset

uspto-grants-2001_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06326501B1