Synthesis
Phosphorus oxychloride (POCl3, 0.418 mL, 3.13 mmol) was slowly added dropwise to N,N-dimethylformamide (DMF, 2.08 mL) at 0°C and under argon protection. After stirring the reaction mixture for 5 min, a DMF solution of 7-nitroindole (200 mg, 1.25 mmol) was added (at a concentration of 10 mL of DMF per 1 g of indole). Subsequently, the reaction mixture was gradually warmed to room temperature and stirring was continued for 3 hours. After completion of the reaction, 3.8 M aqueous potassium hydroxide solution (3.29 mL, 12.5 mmol) was added to the mixture and stirring was continued for 15 hours. Next, saturated aqueous sodium bicarbonate and ethyl acetate (EtOAc) were added to the reaction system until the mixture became clarified, followed by separation of the organic layer. The aqueous phase was extracted with ethyl acetate and the combined organic layers were washed with brine, dried over anhydrous sodium sulfate (Na2SO4), filtered and concentrated under reduced pressure. Finally, the residue was purified by silica gel column chromatography (eluent ratio hexane/ethyl acetate = 1/5) to afford the target product 7-nitroindole-3-carbaldehyde (228 mg, 1.20 mmol, 96% yield) as a yellow amorphous solid.
References
[1] Chemical and Pharmaceutical Bulletin, 2018, vol. 66, # 8, p. 810 - 817
[2] European Journal of Medicinal Chemistry, 2013, vol. 65, p. 158 - 167
[3] Tetrahedron Letters, 2009, vol. 50, # 1, p. 75 - 76
[4] Journal of Medicinal Chemistry, 2008, vol. 51, # 23, p. 7541 - 7551
[5] Journal of Organic Chemistry, 2013, vol. 78, # 6, p. 2362 - 2372
