Synthesis
General procedure for the synthesis of 7-bromo-4-fluoroindole from 2-bromo-5-fluoronitrobenzene and vinylmagnesium bromide:
1. 1.12 g (5 mmol) of 2-bromo-5-fluoronitrobenzene was dissolved in 50 mL of anhydrous THF.
2. The reaction system was cooled to -45 °C under nitrogen protection, and 15 mL of 1 M vinylmagnesium bromide solution in THF was added slowly dropwise, controlling the reaction temperature not to exceed -40 °C. The reaction temperature was then adjusted to -40 °C.
3. After the dropwise addition was completed, the dark-colored reaction solution was continued to be stirred at -40 °C for 30 min.
4. Upon completion of the reaction, the reaction was quenched with 10 mL of saturated aqueous ammonium chloride at -40°C.
5. The reaction mixture was extracted twice with ether and the organic phases were combined.
6. The organic phase was washed once with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered and the solvent was concentrated under reduced pressure.
7. The crude product was dissolved in dichloromethane and purified by silica gel column chromatography (silica gel 100 g, eluent: heptane/ethyl acetate=9:1).
8. 501 mg (47% yield) of 7-bromo-4-fluoro-1H-indole was obtained as an orange oil.
MS (EI): 213.0 (100), 215.0 (100) (M)+.
References
[1] European Journal of Organic Chemistry, 2006, # 13, p. 2956 - 2969
[2] Bioorganic and Medicinal Chemistry, 2015, vol. 23, # 17, p. 5856 - 5869
[3] Patent: US2006/30613, 2006, A1. Location in patent: Page/Page column 35
[4] Bioorganic and Medicinal Chemistry Letters, 2000, vol. 10, # 11, p. 1223 - 1226
[5] Patent: WO2009/153307, 2009, A1. Location in patent: Page/Page column 54
