Ammonium Chloride → 7-bromo-5-fluoro-1H-indole

Temperature

-40 °C

1.22 g (5.0 mmol) of 1-bromo-5-fluoro-2-nitrobenzene were dissolved in 50 ml THF. At a temperature of −45° C. under nitrogen 15 ml (15.0 mmol) of a 1M vinyl magnesium bromide solution in THF were added in such a way, that the temperature was kept below −40° C. The resulting dark solution was stirred for 30 min at −40° C. 10 ml of saturated aqueous NH4Cl solution were added and the reaction mixture was warmed to rt. It was extracted twice with diethyl ether. The organic layer was washed with saturated aqueous NaCl solution, dried over sodium sulfate, filtered and the solvent was evaporated. The residue was purified by column chromatography (100 g silica gel, heptane/EtOAc 9:1) to yield 553 mg (52%) 7-bromo-5-fluoro-indol as a light brown oil. 1H NMR (CDCl3, 300 MHz): δ 8.30 (br s, 1H), 7.29 (m, 1H), 7.25 (m, 1H), 7.16 (m, 1H), 6.60 (m, 1H).

1. customwas kept below −40° C
2. temperaturethe reaction mixture was warmed to rt
3. extractionIt was extracted twice with diethyl ether
4. washThe organic layer was washed with saturated aqueous NaCl solution
5. dry with materialdried over sodium sulfate
6. filtrationfiltered
7. customthe solvent was evaporated
8. customThe residue was purified by column chromatography (100 g silica gel, heptane/EtOAc 9:1)

ORD record

ord-654074d06a9247b890855da621d5b753

Source dataset

uspto-grants-2007_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07259183B2