[Synthesis]
To a dry 100 mL round bottom flask was added 4-bromo-2-fluoro-6-nitrotoluene (1.3 g, 5.56 mmol, 1 eq.), N,N-dimethylformamide diisopropyl acetal (2.6 mL, 12.22 mmol, 2.2 eq.), triethylamine (0.85 mL, 6.11 mmol, 1.1 eq.) and anhydrous DMF (5 mL). The mixture was stirred at 130 °C for 2 hours. Upon completion of the reaction, the solvent was removed under reduced pressure and the residue was dissolved in a solvent mixture of toluene (30 mL) and acetic acid (40 mL). Iron powder (6.2 g, 11.10 mmol, 20 eq.) and silica (6 g) were then added. The dark red mixture was heated to 100 °C under vigorous stirring and maintained for 30 min. After the reaction mixture was cooled to room temperature, it was diluted with EtOAc, filtered and the solid was washed thoroughly with EtOAc. The combined filtrates were washed sequentially with saturated aqueous NaHCO3, aqueous Na2S2O3, saturated aqueous NaHCO3 and brine, dried over Na2SO4 and concentrated under reduced pressure. Purification of the residue by fast column chromatography (20% DCM in hexane solution) afforded 6-bromo-4-fluoro-1H-indole (814 mg, 3.75 mmol, 68% yield; UPLC purity: 99%). |