Sulfuric Acid → 5-Bromo-2-chloro-4-ethoxypyridine

Participants

Reaction Conditions

Reaction Steps

To a mixture of 2-chloro-4-ethoxypyridine (13 g, 82 mmol) and H2SO4 (40 mL, 750 mmol) was added NBS (17.62 g, 99 mmol). Then the mixture was stirred at 60° C. for 10 h. After cooling to rt, the mixture was poured into cold water (300 mL). The mixture was extracted with EA (200 mL×2). The combined organic layer was washed with saturated NaHCO3 solution (200 mL×2) and concentrated. The crude material was purified by silica column chromatography (PE/EA=15:1). All fractions found to contain product by TLC (PE/EA=5:1, Rf=0.6) were combined and concentrated to yield a yellow solid of 5-bromo-2-chloro-4-ethoxypyridine (8.5 g, 26.3 mmol, 32% yield): 1H NMR (400 MHz, CDCl3) δ 8.32 (s, 1H), 6.79 (s, 1H), 4.16 (q, J=6.8 Hz, 2H), 1.50 (t, J=6.8 Hz, 3H); ES-LCMS m/z 238 (M+3).

Provenance & Evidence