Iodine → 3-Iodo-5-methoxy-1-methyl-1H-indole

Participants

Reaction Steps

5-Methoxy-1H-indole (5.00 g, 34.0 mmol) in DMF (100 mL) was stirred with KOH (2.00 g, 35.7 mmol) for about 15 min then iodine (8.80 g, 34.7 mmol) was added. The mixture was stirred for about 30 min then NaH (60% dispersion in mineral oil, 1.63 g, 40.8 mmol) was added portion-wise. After stirring for about 15 min at ambient temperature, iodomethane (2.34 mL, 37.4 mmol) was added and the mixture was stirred for about 2 h. The solvents were removed under reduced pressure and the mixture was stirred with water (300 mL) for about 15 min. The slurry was treated with DCM (100 mL) and the layers were separated. The aqueous layer was extracted with DCM (50 mL) and the combined organics were dried over anhydrous MgSO4, filtered, and concentrated. The material was purified by silica gel chromatography eluting with DCM to give 3-iodo-5-methoxy-1-methyl-1H-indole (9.48 g, 97%): 1H NMR (400 MHz, DMSO-d6 δ 7.48 (s, 1H), 7.38 (d, 1H), 6.86 (dd, 1H), 6.72 (d, 1H), 3.79 (s, 3H), 3.76 (s, 3H); LC/MS (Table 2, Method a) Rt=2.50 min.

Provenance & Evidence