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

Temperatur

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, 1 H), 7.30 (s, 1 H), 7.17 (d, J=1.5 Hz, 1 H), 4.39 (q, J=7.1 Hz, 2 H), 4.05 (s, 3 H), 1.42 (t, J=7.1 Hz, 3 H); 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-Eintrag

ord-5fbf2e7f7dfe4878a2e0fee0f3e89d07

Quelldatensatz

uspto-grants-2010_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07741339B2