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

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.

1. stirringAfter stirring for about 15 min at ambient temperature
2. stirringthe mixture was stirred for about 2 h
3. customThe solvents were removed under reduced pressure
4. stirringthe mixture was stirred with water (300 mL) for about 15 min
5. additionThe slurry was treated with DCM (100 mL)
6. customthe layers were separated
7. extractionThe aqueous layer was extracted with DCM (50 mL)
8. dry with materialthe combined organics were dried over anhydrous MgSO4
9. filtrationfiltered
10. concentrationconcentrated
11. customThe material was purified by silica gel chromatography
12. washeluting with DCM

ORD record

ord-d0db611613274cff93e50edc9b5d578f

Source dataset

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09365579B2