Phosphorus oxychloride → 3-Bromo-2-chloro-4-(4-chlorophenyl)-6-methylpyridine

Participants

Reaction Conditions

Reaction Steps

To a suspension of 3-bromo-4-(4-chlorophenyl)-6-methylpyridin-2(1H)-one (280 mg, 0.94 mmol) in phosphorus oxychloride (5 mL) was added anhydrous DMF (a few drops). The mixture was stirred at 100° C. for 7 h. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure to remove most of the phosphorus oxychloride. The remaining liquid was cooled at 0° C. and carefully quenched by addition of water. The resulting mixture was then adjusted to pH 7-8 by addition of saturated aqueous NaHCO3. The mixture was then extracted with EtOAc (30 mL×3). The combined EtOAc extracts were washed with saturated aqueous NaCl, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified using a silica gel cartridge (12 g) eluted with a gradient of EtOAc (0-70%) in hexanes to obtain 180 mg (60%) of the title compound as a white solid. HPLC/MS: retention time=3.95 min, [M+H]+=316.0.

Provenance & Evidence