5-Bromo-1-methyl-1H-indole

Synthesis

1. 5-bromo-1H-indole (2.08 g, 10.6 mmol) was dissolved in 35 mL of DMF at 0 °C. 2. Sodium hydride (60% dispersed in mineral oil, 467 mg, 11.67 mmol) was added to the above solution, keeping the reaction temperature at 0 °C. 3. After stirring for 30 min, iodomethane (663 μL, 10.6 mmol) was slowly added. 4. The reaction mixture was gradually warmed to room temperature and stirring was continued for 10 min. 5. Upon completion of the reaction, the reaction was quenched with ice water at 0 °C. The reaction was then quenched with ice water. 6. The reaction mixture was extracted with ethyl acetate (3 × appropriate amount). 7. 7. The organic phases were combined, dried over anhydrous magnesium sulfate, filtered and concentrated. 8. The product was purified by fast column chromatography (eluent: 10% ethyl acetate/hexane) to give 5-bromo-1-methyl-1H-indole (2.16 g, 97% yield). 9. The product was analyzed by 1H NMR. 9. The product was characterized by 1H NMR (400 MHz, CDCl3): δ 7.74 (d, J = 1.6 Hz, 1H), 7.30 (dd, J = 8.4, 2.0 Hz, 1H), 7.19 (d, J = 8.8 Hz, 1H), 7.05 (d, J = 3.2 Hz, 1H), 6.42 (d, J = 2.8 Hz, 1H), 3.78 (s, 3H), 6.42 (d, J = 2.8 Hz, 1H) 3.78 (s, 3H).

References

[1] Chemistry Letters, 1991, # 7, p. 1125 - 1128
[2] Bioorganic and Medicinal Chemistry Letters, 1999, vol. 9, # 3, p. 333 - 336
[3] Organic Letters, 2015, vol. 17, # 2, p. 254 - 257
[4] Patent: WO2016/114816, 2016, A1. Location in patent: Paragraph 0332
[5] Bioorganic and Medicinal Chemistry, 2010, vol. 18, # 12, p. 4524 - 4529