Synthesis
GENERAL METHOD: Phosphoryl chloride (0.42 g, 2.74 mmol) was slowly added dropwise to a solution of N,N-dimethylformamide (0.84 g, 11.4 mmol) of 5-fluoroindole (0.30 g, 2.29 mmol) at 0 °C, the dropwise process lasted for 30 min. Subsequently, the reaction mixture was warmed up to 40 °C and kept for 1 hour. Upon completion of the reaction, ice was added to the reaction vessel followed by 2 M sodium hydroxide solution. The mixture was refluxed for 40 minutes. After the reaction solution was cooled to room temperature, it was extracted with ethyl acetate. The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography with the eluent being a mixed solvent of petroleum ether-ethyl acetate to give the target compound 5-fluoroindole-3-carboxaldehyde [19].
References
[1] Archiv der Pharmazie, 2017, vol. 350, # 1,
[2] Journal of the American Chemical Society, 2009, vol. 131, # 31, p. 10796 - 10797
[3] Marine Drugs, 2014, vol. 12, # 4, p. 1757 - 1772
[4] Patent: WO2015/90233, 2015, A1. Location in patent: Paragraph 00263
[5] European Journal of Medicinal Chemistry, 2018, vol. 156, p. 344 - 367
