Sodium hydride → Ethyl 2-(5-nitropyridin-2-YL)acetate

Participants

Reaction Steps

To a suspension of NaH (60% dispersion, 0.900 g, 22.5 mmol) in 40 mL of THF was added malonic acid tert-butyl ester ethyl ester (4.00 mL, 21.1 mmol) and the mixture stirred for 15 min at RT. To this mixture was then added 2-chloro-5-nitro-pyridine (2.56 g, 16.0 mmol) and the reaction stirred for 10 h at RT. The mixture was diluted with 100 mL of EtOAc and washed with NH4Cl (2×100 mL) and brine (100 mL) and dried over Na2SO4 and concentrated in vacuo. The residue was dissolved in DCM (20 mL), TFA (10 mL) was added and the mixture stirred for 2 h at RT. The mixture was concentrated, the residue dissolved in 100 mL of EtOAc and washed with NaHCO3 (2×100 mL) and brine (100 mL) and again dried over Na2SO4 and concentrated in vacuo. The title compound was purified by flash chromatography eluting with 30% EtOAc/hexanes to give 2.35 g (70%) of a light yellow solid. 1H-NMR (CDCl3, 400 MHz): δ 9.38 (d, J=2.6 Hz, 1H), 8.46 (dd, J=8.6, 2.6 Hz, 1H), 7.55 (d, J=8.6 Hz, 1H), 4.22 (q, J=7.1 Hz, 2H), 3.99 (s, 2H), 1.28 (t, J=7.1 Hz, 3H).

Provenance & Evidence