825-70-7

The general procedure for the synthesis of 5-fluoro-2-methylindoline from 5-fluoro-2-methylindole is as follows: Step 1a: 6.22 g of sodium cyanoborohydride was added in four steps to 60 ml of trifluoroacetic acid solution containing 5 g of 5-fluoro-2-methylindole at 5 °C. The reaction mixture was stirred at 0°C for 30 minutes, followed by continued stirring at room temperature for 5 hours. Upon completion of the reaction, the reaction mixture was cooled again and 700 ml of ice water and 150 ml of 31% sodium hydroxide solution were added, followed by 300 ml of ethyl acetate. After stirring for 1 hour at room temperature, the organic phase was separated, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography using 90/10 heptane/ethyl acetate as eluent to give 2.14 g of 5-fluoro-2-methyl-2,3-dihydro-1H-indole. The product was characterized by mass spectrometry (method AR), retention time Tr (min) = 0.24; [M+H]+: m/z 152.

[1] Tetrahedron Asymmetry, 2006, vol. 17, # 17, p. 2558 - 2564
[2] Patent: US2013/274253, 2013, A1. Location in patent: Paragraph 1216-1220
[3] Journal of the American Chemical Society, 2014, vol. 136, # 21, p. 7688 - 7700
[4] Patent: US2016/347678, 2016, A1. Location in patent: Paragraph 0306; 0307