Acetic Acid → Diethyl 2-(5-bromo-3-nitropyridin-2-yl)malonate

Participants

Reaction Steps

To a suspension of NaH (60% in mineral oil, 27.9 g, 0.69 mol) in DMF (300 mL) at 5-10° C. was slowly added ethyl malonate (125 mL, 0.69 mol) over 30 min. The mixture was allowed to stir for 20 min at rt, during which time the suspension became a solution. A solution of 5-bromo-2-chloro-3-nitropyridine (75 g, 0.32 mol) in DMF (75 mL) was added slowly at 5-10° C. The resulting dark red mixture was allowed to stir at 40° C. for 2 h. The reaction mixture was then poured into 1M AcOH (0.75 L) and extracted with DCM (3×250 mL). The organic solutions were combined, washed with water and brine, dried over MgSO4, filtered and concentrated. The residue was purified by column chromatography to give diethyl (5-bromo-3-nitropyridin-2-yl)malonate (260 g, 99%) as a yellow oil.

Provenance & Evidence