6-Bromo-1H-indole

60956-26-5

4637-24-5

52415-29-9

Step A: Under nitrogen protection, 4-bromo-2-nitrotoluene (7.9 g, 36.6 mmol) was dissolved in anhydrous N,N-dimethylformamide (73 mL), and N,N-dimethylformamide dimethyl acetal (14.5 mL, 110 mmol) and pyrrolidine (4.7 mL) were added sequentially. The reaction mixture was heated and stirred in an oil bath at 110 °C for 90 min. After completion of the reaction, the mixture was cooled to room temperature, diluted with ether (200 mL), and washed with deionized water (3 × 100 mL). The organic phases were combined, dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give the crude product. The crude product was dissolved in 80% aqueous acetic acid (245 mL) and heated to 75 °C. Under stirring, zinc powder (20.8 g, 318 mmol) was added in batches for 2 hours. After addition, the reaction mixture was warmed to 85 °C and stirring was continued for 3.5 hours. After completion of the reaction, the mixture was cooled to room temperature and then to 0 °C in an ice bath and filtered to remove insoluble matter. The filtrate was diluted with ethyl acetate (200 mL) and washed with deionized water (2 × 100 mL). The organic phase was dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give a brown oily crude product. The crude product was purified by fast column chromatography with the eluent being a mixed solvent of hexane/ethyl acetate in the order of 95:5 and 90:10 to give 6-bromoindole as a gray solid (2.61 g, 36% yield). The structure of the product was confirmed by 1H NMR (500 MHz, CDCl3): δ 8.14 (br s, 1H), 7.53 (s, 1H), 7.49 (d, J = 8.4 Hz, 1H), 7.21 (dd, J = 8.4, 1.7 Hz, 1H), 7.17-7.15 (m, 1H), 6.53-6.51 (m, 1H).