5-Chloro-6-fluoro-1H-indole

Application

Synthesis

1097107-68-0

169674-57-1

General procedure for the synthesis of 5-chloro-6-fluoroindole from methyl (4-chloro-5-fluoro-2-((trimethylsilyl)ethynyl)phenyl)carbamate: dissolve the crude (4-chloro-5-fluoro-2-trimethylsilylethynylphenyl)carbamate methyl ester (ca. 21 mmol) in tetrahydrofuran (200 mL) and add tetrabutylammonium fluoride (43.3 mL, 1 M in tetrahydrofuran, 43.3 mmol). The reaction was carried out at room temperature. After stirring for 5 minutes, the reaction mixture was refluxed for 1 hour under argon protection. After completion of the reaction, the mixture was cooled to room temperature and concentrated under reduced pressure. The resulting oil was treated with water (55 mL), stirred for 10 minutes and subsequently extracted twice with ethyl acetate (100 mL). The combined organic phases were washed sequentially with 1 M aqueous hydrochloric acid (50 mL), saturated aqueous sodium bicarbonate (50 mL), and saturated aqueous sodium chloride (50 mL), and finally dried with magnesium sulfate. The dried organic phase was filtered and concentrated under reduced pressure. The residue was stirred with hexane (200 mL) under reflux, cooled to 5 °C and filtered to afford 5-chloro-6-fluoro-1H-indole (3.15 g, 85% yield) as a light brown solid. Mass spectrometry (EI) showed a molecular ion peak m/z 169.1 (M+).

References