Hydrochloric Acid → 3-Bromo-6-chloro-2,4-dimethylpyridine

Participants

Reaction Conditions

Reaction Steps

A stirred solution of 2-amino-5-bromo-4,6-dimethylpyridine (65 g, 323 mmol) in 37% hydrochloric acid (780 ml) was cooled to −10° C. Sodium nitrite (66.9 g, 970 mmol) was added in small portions over 10 min. The reaction was stirred for 15 min at −10° C. and then warmed to room temperature. After stirring for 1 hour at r.t., the reaction was quenched by pouring into ice/water (4 L). The mixture was stirred for 5 minutes and then extracted with EtOAc (4 L). The organic extract was washed with water (4 L) and brine (2 L). The organic layer was dried over Na2SO4, filtered, and concentrated. The resulting white solid was dissolved in CH2Cl2 (200 mL) and heptanes (700 mL) were added. The solution was stirred for 20 minutes and then filtered to remove solids. The filtrate was concentrated and the residue was purified by flash chromatography on silica gel with 0 to 15% EtOAc/heptanes to afford 3-bromo-6-chloro-2,4-dimethylpyridine. LCMS=219.9 and 221.9 (M+H)+ 1H NMR (CDCl3, 500 MHz) δ 7.05 (s, 1H), 2.65 (s, 3H), 2.39 (s, 3H).

Provenance & Evidence