Methyl iodide → Methyl N-methylindole-6-carboxylate

Temperature

0 °C

A solution of 1H-indole-6-carboxylic acid (2.60 g, 16.1 mmol) in tetrahydrofuran (100 mL) and diethyl ether (100 mL) was treated with ethereal diazomethane until tlc indicated complete consumption of the starting material. After the solution was allowed to stand overnight, the solvent was evaporated under reduced pressure and the resulting residue was dissolved in tetrahydrofuran (100 mL). The solution was cooled to ˜0° C. and sodium hydride (60% suspension in mineral oil; 2.00 g, 50.0 mmol) and then iodomethane (10.00 g, 70.5 mmol) were added. and the reaction mixture was stirred at room temperature overnight. Water (200 mL) was added, carefully at first and the mixture was extracted with ethyl acetate (2×200 mL). The combined ethyl acetate layers were washed with brine (100 mL), dried (MgSO4), filtered and concentrated in vacuo. The crude product was chromatographed over silica gel (30-50% ethyl acetate/hexanes) to furnish 1-methyl-1H-indole-6-carboxylic acid methyl ester (2.52 g, 83% yield) as a yellow oil that solidified on standing.

1. customconsumption of the starting material
2. customthe solvent was evaporated under reduced pressure
3. dissolutionthe resulting residue was dissolved in tetrahydrofuran (100 mL)
4. extractioncarefully at first and the mixture was extracted with ethyl acetate (2×200 mL)
5. washThe combined ethyl acetate layers were washed with brine (100 mL)
6. dry with materialdried (MgSO4)
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customThe crude product was chromatographed over silica gel (30-50% ethyl acetate/hexanes)

ORD record

ord-2c06062cb2e74c3d87c7038c6676e00a

Source dataset

uspto-grants-2003_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06515124B2