Isopropyl iodide → 1-[6-Chloro-1-(1-methylethyl)-1H-indol-3-yl]-2,2,2-trifluoroethanone

Temperature

25 °C

A solution of 1-(6-chloro-1H-indol-3-yl)-2,2,2-trifluoro-ethanone in N,N-dimethylformamide (5 mL) was treated with potassium carbonate (698 mg, 5.05 mmol). The reaction was stirred at 25° C. for 15 min and then was treated with 2-iodopropane (0.30 mL, 3.03 mmol). This mixture was heated at 65° C. for 20 h. At this time, the reaction was cooled to 25° C., quenched with water (5 mL), and then partitioned between water (50 mL) and ethyl acetate (50 mL). This mixture was treated with a saturated aqueous sodium chloride solution (1×25 mL), shaken, and separated. The organic layer was then dried over magnesium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40M, Silica, 3/1 hexanes/ethyl acetate) afforded 1-(6-chloro-1-isopropyl-1H-indol-3-yl)-2,2,2-trifluoro-ethanone (483 mg, 83%) as a pale pink solid: mp 94-96° C.; EI-HRMS m/e calcd for C13H11ClF3NO (M+) 289.0481, found 289.0482.

1. temperatureThis mixture was heated at 65° C. for 20 h
2. temperatureAt this time, the reaction was cooled to 25° C.
3. customquenched with water (5 mL)
4. custompartitioned between water (50 mL) and ethyl acetate (50 mL)
5. additionThis mixture was treated with a saturated aqueous sodium chloride solution (1×25 mL)
6. stirringshaken
7. customseparated
8. dry with materialThe organic layer was then dried over magnesium sulfate
9. filtrationfiltered
10. concentrationconcentrated in vacuo

ORD record

ord-ede64a794ac54c108011d710043f3c20

Source dataset

uspto-grants-2005_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06881844B2