Diethyl Malonate → 5-Nitro-2,3-dihydro-1H-indene-2-carboxylic acid

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Reaction Steps

Diethyl malonate (9.10 mL, 60.0 mmol) was added to a stirred suspension of NaH (60% in oil, 3.02 g, 126 mmol) in dry Et2O (500 mL) at 20° C. under N2 and the mixture was stirred for 30 min. 1,2-Bis(bromomethyl)-4-nitrobenzene (118) (18.5 g, 60.0 mmol) was added and the mixture was stirred at 20° C. for 24 h. The reaction was diluted with EtOAc (200 mL) and washed with 1 M HCl. The solvent was evaporated to give a brown oil that was treated with 2 M NaOH (100 mL) in EtOH (100 mL) at 20° C. for 15 h. Most of the solvent was evaporated and DCM (300 mL) was added and the mixture was acidified with 1 M HCl. The organic fraction was dried and the solvent evaporated to give a brown solid that was suspended in xylene (200 mL) and stirred at reflux temperature for 90 min. The solvent was evaporated to give a brown oil which was purified by chromatography, eluting with a gradient (0-20%) of EtOAc/pet. ether, to give acid 119 (2.44 g, 20%) as a pale yellow solid: mp (EtOAc/pet. ether) 115-117° C.; 1H NMR δ 9.10 (br s, 1H, CO2H), 8.06-8.11 (m, 2H, H-4, H-6), 7.36 (d, J=9.0 Hz, 1H, H-7), 3.30-3.56 (m, 5H, H-1, H-2, H-3); 13C NMR δ 180.0, 149.0, 147.6, 143.1, 124.8, 122.7, 119.6, 43.3, 35.9, 35.7. Anal. calcd for C10H9NO4: C, 58.0; H, 4.4; N, 6.8. Found: C, 58.2; H, 4.5; N, 6.8%.

Provenance & Evidence