Synthesis
General procedure for the synthesis of 4-chloro-7-bromoindole from 2-bromo-5-chloronitrobenzene and vinylmagnesium bromide: 1.19 g (5 mmol) of 2-bromo-5-chloronitrobenzene was dissolved in 50 mL of anhydrous THF. Under the protection of nitrogen, 15 mL of 1 M vinylmagnesium bromide in THF solution was added slowly dropwise at -45 °C, and the reaction temperature was controlled not to exceed -40 °C. The reaction was carried out at -40 °C. After the dropwise addition was completed, the resulting dark-colored reaction solution was continued to be stirred at -40 °C for 30 min. Upon completion of the reaction, the reaction was quenched with 10 mL of saturated aqueous ammonium chloride solution at -40 °C, followed by two extractions with ether. The organic phases were combined, washed once with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by column chromatography (100 g silica gel, eluent heptane/ethyl acetate 19:1) to give 562 mg (49% yield) of 7-bromo-4-chloro-1H-indole as an orange oil. Mass spectral (EI) data: m/z 229.0 (80%), 231.0 (100%), 233.0 (30%) (M+).
References
[1] Patent: US2006/30613, 2006, A1. Location in patent: Page/Page column 35
[2] Patent: WO2016/16370, 2016, A1. Location in patent: Page/Page column 39; 40
[3] Patent: US2014/274695, 2014, A1. Location in patent: Paragraph 0292; 0293
[4] Patent: KR101601357, 2016, B1. Location in patent: Paragraph 0328-0330
[5] Bioorganic and Medicinal Chemistry Letters, 2000, vol. 10, # 11, p. 1223 - 1226
