Phenol → 8-Bromo-3-methyl-2-phenoxyquinoline

Participants

Reaction Conditions

Reaction Steps

Phenol (954 mg, 10.14 mmol) was added to a suspension of NaH (60% w/w in mineral oil; 406 mg, 10.14 mmol) in DMF (10 mL) at 0° C. and the resulting solution was stirred at 25° C. for 15 min. 8-Bromo-2-chloro-3-methylquinoline (510 mg, 1.988 mmol) was then added, and the resulting solution was heated at 60° C. for 2.5 d. The mixture was cooled to 25° C. and partitioned between EtOAc (100 mL) and saturated aq. NH4Cl (80 mL). The organic layer was separated, sequentially washed with water (2×50 mL) and brine (50 mL), dried over Na2SO4, filtered, and concentrated in vacuo. Chromatographic purification of the residue (silica gel, 0-10% EtOAc/hexanes) furnished 8-bromo-3-methyl-2-phenoxyquinoline (505.5 mg, 1.609 mmol, 81% yield) as a colorless oil, which was used without further purification in the subsequent step: m/z (ESI, +ve) 314.0 (M+H)+.

Provenance & Evidence