2-Bromobutane → Methyl 6-bromo-1-(sec-butyl)-1H-indole-4-carboxylate

To a stirred suspension of sodium hydride (5.66 g, 141.7 mmol) in DMF (100 mL) was added a solution of methyl 6-bromo-1H-indole-4-carboxylate (4) (30 g, 118.1 mmol) in DMF (50 mL) at 0° C. and stirred for 20 min. Then 2-Bromo butane (29.1 g, 212.5 mmol) was added at 0° C. and the reaction mixture was stirred at room temperature for 16 h. The reaction mixture was diluted with cold water and extracted with ethyl acetate (4×150 mL). The combined organic layer was washed with cold water (150 mL), brine (100 mL) and dried over anhydrous Na2SO4 and concentrated under reduced pressure to afford crude, which was purified by column chromatography over silica gel (60-120 mesh) using 5% EtOAc: Pet ether as eluent to afford the title compound methyl 6-bromo-1-sec-butyl-1H-indole-4-carboxylate, (14 g, 40.1%) as pale yellow solid. 1H NMR (CDCl3, 400 MHz) δ 0.843-0.870 (m, 3H), 1.512 (d, J=6.4 Hz, 3H), 1.844-1.926 (m, 2H), 3.976 (s, 3H), 4.333-4.385 (m, 1H), 7.132 (d, J=3.2 Hz, 1H), 7.302 (d, J=3.6 Hz, 1H), 7.707 (s, 1H), 7.984 (d, J=1.6 Hz, 1H).

1. stirringthe reaction mixture was stirred at room temperature for 16 h
2. extractionextracted with ethyl acetate (4×150 mL)
3. washThe combined organic layer was washed with cold water (150 mL), brine (100 mL)
4. dry with materialdried over anhydrous Na2SO4
5. concentrationconcentrated under reduced pressure
6. customto afford crude, which
7. customwas purified by column chromatography over silica gel (60-120 mesh)

ORD record

ord-3c71dfb3c161434ebc3df68e6ccd9787

Source dataset

uspto-grants-2013_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08536179B2