Isopropyl iodide → 2,2,2-trifluoro-1-(1-isopropyl-6-methyl-1H-indol-3-yl)-ethanone

Temperature

25 °C

A solution of 2,2,2-trifluoro-1-(6-methyl-1H-indol-3-yl)-ethanone (1.5 g, 6.60 mmol) in N,N-dimethylformamide (15 mL) at 25° C. was treated with potassium carbonate (2.28 g, 16.51 mmol). The resulting mixture was stirred at 25° C. for 15 min and then treated with 2-iodopropane (0.99 mL, 9.90 mmol). The reaction was heated at 65° C. for 3 h. At this time, the reaction was cooled to 25° C. and was partitioned between water (100 mL) and ethyl acetate (100 mL). The organic layer was then washed with a 1N aqueous hydrochloric acid solution (1×50 mL) and a saturated aqueous sodium chloride solution (1×50 mL), dried over magnesium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40M, Silica, 4/1 hexanes/ethyl acetate) afforded 2,2,2-trifluoro-1-(1-isopropyl-6-methyl-1H-indol-3-yl)-ethanone (1.61 g, 90.6%) as a pink solid: mp 65-68° C.; EI-HRMS m/e calcd for C14H14F3NO (M+) 269.1027, found 269.1037.

1. temperatureThe reaction was heated at 65° C. for 3 h
2. temperatureAt this time, the reaction was cooled to 25° C.
3. customwas partitioned between water (100 mL) and ethyl acetate (100 mL)
4. washThe organic layer was then washed with a 1N aqueous hydrochloric acid solution (1×50 mL)
5. dry with materiala saturated aqueous sodium chloride solution (1×50 mL), dried over magnesium sulfate
6. filtrationfiltered
7. concentrationconcentrated in vacuo

ORD record

ord-180288b78e12416ab698c7bba592a598

Source dataset

uspto-grants-2005_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06881844B2