Diethyl Malonate → 5-Bromo-2-methyl-3-nitropyridine

Participants

Reaction Steps

To a suspension of NaH 55% in oil (300 mg, 6.87 mmol) in 6 ml DMF was added dropwise diethyl malonate (Aldrich, Buchs, Switzerland, 1.0 g, 6.24 mmol). The reaction mixture was stirred for 20 min at rt before adding 5-bromo-2-chloro-3-nitropyridine (Matrix, Columbia, USA, 1.19 g, 5.0 mmol). The reaction mixture was stirred for 30 min at rt and for 1 h at 40° C. The reaction mixture was quenched with 10% aqueous NH4Cl and extracted with EtOAc (2×). The combined organic layers were washed with brine (4×), dried over Na2SO4, filtered and evaporated. The residue was stirred in concentrated HCl (20 ml) for 13 h at 100° C. After cooling, the reaction mixture was basified with 10 M aqueous NaOH and extracted with EtOAc (2×). The organic layers were washed with brine, dried over Na2SO4, filtered and evaporated. The residue was dry loaded on silica gel and purified by MPLC (heptane/EtOAc 0% to 15%) to give the title compound as a yellow solid. (HPLC: tR 2.84 (Method A).

Provenance & Evidence