Nitrobenzene → 7-bromo-4-fluoro-1H-indole

Temperature

-40 °C

A solution of 2-bromo-5-fluoronitrobenzene (4.4 g, 20 mmol) in dry THF (200 mL) under N2 was cooled to −65° C. (acetone/CO2). A solution of vinylmagnesium bromide (60 mL, 1 M, 60 mmol) in THF was added to the nitrobenzene solution as rapidly as possible maintaining the reaction temperature below −40° C. After addition of the Grignard reagent, the cooling bath was switched to a −40° C. bath (CH3CN/CO2), and the mixture was stirred at −40° C. for 30 min. The reaction mixture was quenched with sat. NH4Cl solution (500 mL) and extracted with ether (2×200 mL), then dried (brine, Na2SO4) and concentrated in vacuo. The resulting material was purified by SiO2 flash column chromatography (5:95) EtOAc/Hexanes to give 4-fluoro-7-bromoindole, as a light brown oil (2.03 g, 9.5 mmol, 54%). 1H NMR (CDCl3) δ 6.72 (m, 2H), 7.24 (m, 2H), 8.4 (br s, 1H). MS m/e 215 (MH+).

1. temperatureas possible maintaining the reaction temperature below −40° C
2. customwas switched to a −40° C.
3. customThe reaction mixture was quenched with sat. NH4Cl solution (500 mL)
4. extractionextracted with ether (2×200 mL)
5. dry with materialdried (brine, Na2SO4)
6. concentrationconcentrated in vacuo
7. customThe resulting material was purified by SiO2 flash column chromatography (5:95) EtOAc/Hexanes

ORD record

ord-39989d5f4f874f1ca7b3d1231c541b95

Source dataset

uspto-grants-2003_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06573262B2