4-methyl-7-nitro-1H-indole-3-carbaldehyde

Synthesis

To 12 mL (154 mmol) of N,N-dimethylformamide was slowly added 1.5 mL (16.1 mmol) of phosphoryl chloride at 0 °C, kept at 0 °C and stirred for 20.5 hours. Subsequently, 2.0 g (11.4 mmol) of 4-methyl-7-nitro-1H-indole dissolved in 20 mL of N,N-dimethylformamide was added dropwise to the reaction mixture at the same temperature. The reaction system was warmed up to 90 °C with continuous stirring for 21 hours. Upon completion of the reaction, the reaction mixture was cooled to 0 °C and the reaction was quenched by the addition of 100 mL of aqueous 1N sodium hydroxide solution. The reaction mixture was extracted with ethyl acetate, the organic phase was washed sequentially with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to remove the solvent. A mixed solvent of tert-butyl methyl ether and hexane was added to the residue, a solid was precipitated, and the crystals were collected by filtration to give 2.23 g of 4-methyl-7-nitro-1H-indole-3-carbaldehyde in 95.8% yield. The product was characterized by 1H-NMR (DMSO-d6): δ 2.90 (3H, s), 7.21 (1H, d, J = 8.4 Hz), 8.11 (1H, d, J = 8.4 Hz), 8.39 (1H, s), 10.01 (1H, s), 12.71 (1H, br s).

References

[1] Patent: US2007/37854, 2007, A1. Location in patent: Page/Page column 5