Synthesis
4-Bromo-1-methyl-2-nitrobenzene (11.57 mmol, 2.5 g) was dissolved in tetrahydrofuran (THF, 116 mL) under nitrogen protection and cooled to -40 °C. Vinylmagnesium bromide (46.28 mmol, 46 mL) was added slowly, keeping the reaction temperature at -40 °C. The reaction mixture was stirred at this temperature for 40 min before the reaction was quenched with saturated aqueous ammonium chloride (NH4Cl). The aqueous layer was separated and extracted with ethyl acetate (2×). The organic layers were combined, dried with anhydrous sodium sulfate (Na2SO4), filtered and the solvent was concentrated. The crude product obtained was dissolved in THF (35 mL) and cooled to 0 °C. 0.5 N hydrochloric acid (HCl, 4.4 mL) was added slowly and the reaction mixture was stirred at 0 °C for 1 hour. Subsequently, the reaction was quenched with aqueous sodium bicarbonate (NaHCO3, 44 mL). The aqueous layer was separated and extracted with ethyl acetate (2×). The organic extracts were combined, dried with anhydrous sodium sulfate (Na2SO4), filtered and the solvent concentrated. The crude product was purified by fast column chromatography on silica gel, the eluent being a hexane solution of 11% ethyl acetate to give the pure 4-bromo-7-methyl-1H-indole (1.05 g, yield: 43%). The structure of the product was confirmed by 1H NMR (400 MHz, CDCl3) and LC-MS: 1H NMR δ 8.21 (1H, brs), 7.28-7.26 (1H, m), 7.21 (1H, d, J = 7.2 Hz), 6.87 (1H, d, J = 6.8 Hz), 6.63-6.61 (1H, m), 2.47 (3H, s); LC-MS: tR = 3.58 min, [M + H]+ not detected (Method 3).
References
[1] Patent: WO2013/149997, 2013, A1. Location in patent: Page/Page column 120-121
[2] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2016, vol. 55B, # 9, p. 1117 - 1130
[3] Patent: WO2007/122410, 2007, A1. Location in patent: Page/Page column 93
