Ammonium Hydroxide → 7-Bromo-8-fluoro-2-methylquinoline

Participants

Reaction Conditions

Reaction Steps

A solution of tert-butyl 3-bromo-2-fluorophenylcarbamate (6.0 g, 20.7 mmol) in 4N HCl (30 mL) in dioxane was stirred at ambient temperature for 2 hours. The solvent was removed under reduced pressure. The residue was dissolved in 6 N HCl (100 mL) and (E)-but-2-enal (2.96 ml, 36.2 mmol) was added dropwise at 106° C. The reaction was stirred at 106° C. for 2 hours. After cooling to ambient temperature, the reaction mixture was basified with ammonium hydroxide to about pH 12, extracted with DCM (2×100 mL), dried (sodium sulfate), filtered and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (5:1 hexane/ethyl acetate) to give 7-bromo-8-fluoro-2-methylquinoline (2.99 g, 60.2%) as a solid.

Provenance & Evidence