Hydrochloric Acid → Dimethyl (4-carboxy-2-nitrophenyl)malonate

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Reaction Steps

Sodium hydride (13.5 g of a 60% dispersion in oil, 0.34 mol) was washed with petroleum ether (×3) under nitrogen and suspended in dry THF (400 mL). A solution of dimethyl malonate (40.4 mL, 0.35 mol) in THF (50 mL) was added dropwise over 45 min with water-bath cooling, keeping the internal temperature below 30° C., and the resulting gel was broken up with more dry THF (300 mL). The above t-Butyl 4-chloro-3-nitrobenzoate (21.7 g, 84 mmol) was added and the mixture was stirred at reflux under nitrogen for 15 h. The red-brown solution was cooled, poured into water, and aqueous HCl (2 N, ca. 60 mL) added slowly until the red nitronate color was dispersed. The THF was evaporated and the aqueous phase extracted with CH2Cl2 (×3), the extracts were dried (Na2SO4) and evaporated. Formic acid (100 mL) was added to the residue and the mixture was stirred at 50° C. for 4 h (when tlc analysis showed no remaining t-butyl ester). The formic acid was evaporated and the residue was taken up in EtOAc and washed with water (×3). The organic layer was extracted with aqueous NaHCO3 (×2), and the aqueous phase was acidified (conc. HCl), and extracted with CH2Cl2 (×2). The organic layer was dried (Na2SO4), evaporated, and the resulting cream solid recrystallized from benzene (ca. 250 mL) to give dimethyl (4-carboxy-2-nitrophenyl)malonate as cream prisms (21.8 g, 87%), mp 147-149° C. 1H NMR ((CD3)2SO) d 13.77 (br s, 1 H, CO2H), 8.52 (d, J=1.7Hz, 1 H, H-3), 8.28 (dd, J=8.1, 1.7 Hz, 1 H, H-5), 7.70 (d, J=8.1 Hz, 1 H, H-6), 5.62 (s, 1 H, ArCH), 3.71 (s, 6 H, CO2Me); 13C NMR ((CD3)2SO) d 166.9, 165.1, 148.2, 134.0, 133.1, 132.3, 132.1, 125.5 (CO2Me, C-1,2,3,4,5,6), 54.3 (ArCH), 52.9 (OMe). Anal. Calculated for C12H11NO8 : C, 48.5; H, 3.7; N, 4.7. Found: C, 48.7; H, 3.5; N, 4.7%.

Provenance & Evidence