Bromoform → 2-(Dibromomethyl)-6-methoxy-5-methyl-3-nitropyridine

Participants

Reaction Steps

To a 3 neck, 22 L round bottom flask equipped with a mechanical stirrer and an addition funnel was added potassium t-butoxide (450 g, 4.00 mol) and THF (4 L). The mixture was stirred vigorously and a solution of 2-methoxy-3-methyl-5-nitropyridine (100 g, 0.595 mol) from Part I and bromoform (195.4 g, 0.773 mol) in 500 mL of dry THF was added dropwise at such a rate that the temperature did not rise above −74° C. (3 h addition time). The reaction mixture was stirred at −78° C. for an additional 15 min. The reaction mixture was then quenched by the dropwise addition of a mixture of methanol (400 ml) and conc. HCl (600 mL) while maintaining the temperature below −68° C. Water (1 L) was then added and the aqueous layer was extracted with EtOAc (3×4 L). The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated. The product was purified by column chromatography on silica gel (0%→7% ethyl acetate in hexanes) to give 2-(dibromomethyl)-6-methoxy-5-methyl-3-nitropyridine (190.0 g, 94% yield) as a red-brown solid: mp 58.7-61.2° C. 1H NMR (300 mHz, CDCl3) δ 8.04 (s, 1H), 7.60 (s, 1H), 4.15 (s, 3H), 2.26 (s, 1H); LRMS, (ESI) m/e 339.0 [(M+H)+, calcd for C8H9N2O3Br2, 338.9].

Provenance & Evidence