Uses
5-Methoxy-1-methylindole-3-carboxaldehyde is used as an important raw material and intermediate used in organic Synthesis, pharmaceuticals, agrochemicals and dyestuff.
Synthesis
1. 5-methoxyindole-3-carboxaldehyde (300 mg, 1.71 mmol) was added to a stirring solution of sodium hydride suspension (82 mg, 2.05 mmol, 60% dispersed in mineral oil) in DMF (8 mL) in batches under argon protection, a process which needed to be completed within 5 minutes.
2. The reaction mixture was continued to be stirred for 30 minutes, followed by the addition of iodomethane (0.13 mL, 2.05 mmol) and continued stirring for 1 hour.
3. Upon completion of the reaction, 10% sodium bicarbonate solution (40 mL) was added and the mixture was extracted with ethyl acetate (4×).
4. The organic layers were combined, washed sequentially with 10% sodium bicarbonate solution (2×) and saturated sodium chloride solution, dried over anhydrous magnesium sulfate, filtered and concentrated.
5. The crude product was purified by column chromatography (eluent: 50:50 ethyl acetate/hexane) to afford 5-methoxy-1-methylindole-3-carbaldehyde (320 mg, 99%) as a light yellow solid.
Rf = 0.35 (50:50 ethyl acetate/hexane); melting point = 130-132°C (literature value: 132-133°C).
1H NMR (CDCl3): δ 9.95 (s, 1H), 7.79 (d, 1H, J = 2.4 Hz), 7.62 (s, 1H), 7.25 (d, 1H, J = 8.8 Hz), 6.96 (dd, 1H, J = 2.4 and 8.9 Hz), 3.90 (s, 3H), 3.85 (s, 3H).
References
[1] Tetrahedron, 2005, vol. 61, # 7, p. 1793 - 1801
[2] Organic Letters, 2013, vol. 15, # 11, p. 2636 - 2639
[3] Patent: US2003/8850, 2003, A1
[4] Journal of Medicinal Chemistry, 2018, vol. 61, # 14, p. 6261 - 6276
[5] Chemical Biology and Drug Design, 2015, vol. 86, # 4, p. 731 - 745
