Methyl iodide → 3-Bromo-1-methyl-6-nitro-1H-indole

Method A Add 1M lithium hexamethyldisilazide in tetrahydrofuran (31.2 mL, 31.17 mmol) and methyl iodide (2.6 mL, 41.56 mmol) to a solution of 3-bromo-6-nitro-1H-indole 2 (5.01 g, 20.78 mmol) in N,N-dimethylformamide (100 mL) at 0° C. Warm the reaction mixture to room temperature and allow it to stir for 5 hr. Quench with saturated aqueous ammonium chloride (100 mL), dilute with ethyl acetate (200 mL), and separate the layers. Sequentially, wash the organic layer with 10% aqueous lithium chloride (75 mL), saturated aqueous sodium bicarbonate (75 mL), water (75 mL×2), and brine (75 mL). Dry the resulting organic layer over Na2SO4 and filter. Concentrate the filtrate to provide a residue. Adsorb the residue with the crude product onto silica gel. Chromatograph the residue on a silica gel column eluting with dichloromethane in hexane (5-50 v/v %) to give 4.13 g of the title compound (78%). LRMS (API ES+)=255.0 (M+H).

1. customat 0° C
2. customQuench with saturated aqueous ammonium chloride (100 mL)
3. additiondilute with ethyl acetate (200 mL)
4. customseparate the layers
5. washSequentially, wash the organic layer with 10% aqueous lithium chloride (75 mL), saturated aqueous sodium bicarbonate (75 mL), water (75 mL×2), and brine (75 mL)
6. dry with materialDry the resulting organic layer over Na2SO4
7. filtrationfilter
8. concentrationConcentrate the filtrate
9. customto provide a residue
10. washChromatograph the residue on a silica gel column eluting with dichloromethane in hexane (5-50 v/v %)

ORD record

ord-c07dee49be874f0c90df307cc3c87e33

Source dataset

uspto-grants-2011_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07932284B2