Bromide ion → 3-bromo-4-(4-chlorophenyl)-6-methylpyridin-2(1H)-one

Participants

Reaction Conditions

Reaction Steps

A suspension of 4-(4-chlorophenyl)-6-methylpyridin-2(1H)-one (0.44 g, 2.0 mmol) in methanol (30 mL) was refluxed until a clear solution formed. The solution was allowed to cool to 40° C., then NBS (285 mg, 1.6 mmol) was added in small portions over 30 min. After completion of the addition, analysis by HPLC/MS indicated about 40% of the starting 4-(4-chlorophenyl)-6-methylpyridin-2(1H)-one remained. Additional NBS (142 mg, 0.8 mmol) was added in portions over 10 min. The reaction mixture was stirred at room temperature for 1 h, then concentrated under reduced pressure. The residue was triturated with a mixture of water (50 mL) and EtOAc (50 mL), and filtered to obtain a solid product which contained mainly the regioisomeric bromide, 5-bromo-4-(4-chlorophenyl)-6-methylpyridin-2(1H)-one. The filtrate was extracted with EtOAc (30 mL×3). The combined extracts were washed with aqueous saturated NaCl solution, dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was purified using a silica gel cartridge (80 g) eluted with a gradient of EtOAc (30-100%) in hexanes to afford 280 mg (47%) of the title product as a white solid. HPLC/MS: retention time=3.15 min, [M+H]+=298.0.

Provenance & Evidence