Methyl iodide → ethyl 4,6-dichloro-1-methyl-1H-indole-2-carboxylate

Temperature

0 °C

NaH (60% dispersion in mineral oil, 0.24 g, 6 mmole) was washed with hexanes, then was suspended in anhydrous DMF (16 mL). The mixture was cooled to 0° C., and ethyl 4,6-dichloroindole-2-carboxylate (1.03 g, 4 mmole) was added. After 2-3 min, iodomethane (1.3 mL, 20 mmole) was added, and the mixture was warmed to RT. The mixture became thick, and stirring became difficult for several minutes. After 0.5 hr, the reaction was cooled to 0° C. and quenched with 10% NH4Cl (2 mL). The mixture was concentrated to dryness, and the residue was partitioned between Et2O (50 mL) and H2O (10 mL). The layers were separated and the organic layer was washed with H2O (5 mL), dried (MgSO4), and filtered, and the filter pad was washed with a little CH2Cl2. Concentration afforded the title compound (1.06 g, 97%) as an off-white solid: 1H NMR (400 MHz, CDCl3) δ 7.34 (s, 1H), 7.30 (s, 1H), 7.17 (d, J=1.5 Hz, 1H), 4.39 (q, J=7.1 Hz, 2H), 4.05 (s, 3H), 1.42 (t, J=7.1 Hz, 3H); MS (ES) m/e 272 and 274 (M+H)+.

1. temperaturethe mixture was warmed to RT
2. waitbecame difficult for several minutes
3. waitAfter 0.5 hr
4. temperaturethe reaction was cooled to 0° C.
5. customquenched with 10% NH4Cl (2 mL)
6. concentrationThe mixture was concentrated to dryness
7. customthe residue was partitioned between Et2O (50 mL) and H2O (10 mL)
8. customThe layers were separated
9. washthe organic layer was washed with H2O (5 mL)
10. dry with materialdried (MgSO4)
11. filtrationfiltered
12. washthe filter pad was washed with a little CH2Cl2
13. concentrationConcentration

ORD record

ord-1273e97d24104434b7300b3be9ccdf5e

Source dataset

uspto-grants-2007_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07250424B2