Synthesis
General procedure for the synthesis of 5-fluoro-1H-indole-3-carboxylic acid from 2,2,2-trifluoro-1-(5-fluoro-1H-indol-3-yl)ethanone: 2,2,2-trifluoro-1-[5-fluoro-1-(pyrimidin-2-yl)-1H-indol-3-yl]ethan-1-one (1.6 g) and 5 N aqueous sodium hydroxide were added to the reaction flask. The reaction mixture was stirred under heated reflux conditions for 1.5 hours. After completion of the reaction, the reaction solution was cooled to room temperature and extracted by adding water and ethyl acetate. After separating the organic and aqueous layers, the aqueous layer was made acidic with concentrated hydrochloric acid. The acidic aqueous layer was again extracted with ethyl acetate, the organic layers were combined and washed with saturated saline. The organic layer was dried with anhydrous sodium sulfate and the solvent was removed by distillation under reduced pressure to give 785 mg of 5-fluoro-1H-indole-3-carboxylic acid (88% yield).
References
[1] Journal of Medicinal Chemistry, 2014, vol. 57, # 17, p. 7293 - 7316
[2] Patent: EP2548864, 2013, A1. Location in patent: Paragraph 0178; 0179
[3] Patent: WO2013/14102, 2013, A1. Location in patent: Page/Page column 26; 32; 33
[4] Patent: JP2017/171619, 2017, A. Location in patent: Paragraph 0168; 0170
