Synthesis
General procedure for the synthesis of 6-chloroindole-3-carboxylic acid from 1-(6-chloro-3-indolyl)-2,2,2-trifluoroethanone:
b) 21.6 g (87.2 mmol) of 1-(6-chloro-1H-indol-3-yl)-2,2,2-trifluoroethanone was dissolved in 110 mL of aqueous 4 M potassium hydroxide solution and heated to reflux for 2 hours. Upon completion of the reaction, the reaction solution was cooled to 0 °C and neutralized with 36.7 mL of concentrated aqueous hydrochloric acid, at which point a white solid precipitated from the solution. The solid product was collected by filtration and washed with deionized water. Finally, the product was dried under high vacuum at 80 °C to give 16.4 g (96% yield) of 6-chloroindole-3-carboxylic acid as a light yellow solid. Mass spectrometry result: m/e 194 (M-H+, 100%).
References
[1] Patent: US2007/72888, 2007, A1. Location in patent: Page/Page column 14-15
[2] Journal of Medicinal Chemistry, 2015, vol. 58, # 5, p. 2275 - 2289
[3] Patent: JP2017/171619, 2017, A. Location in patent: Paragraph 0133; 0135
[4] Patent: EP2548864, 2013, A1. Location in patent: Paragraph 0175
[5] Patent: WO2013/14102, 2013, A1. Location in patent: Page/Page column 26; 32
