Hydrochloric Acid → Methyl 2-amino-5-cyanobenzoate

Participants

Reaction Steps

A mixture of 2-amino-5-bromo-benzoic acid methyl ester (5.00 g, 21.7 mmol) and CuCN (2.34 g, 26.1 mmol, 2.0 M) in 25 ml of NMP was stirred at reflux for 5 h, then cooled to rt. The mixture was poured into a solution of hydrated FeCl3 (15 g of FeCl3.6H2O) and conc. HCl (2.2 ml) in 15 ml of H2O. The resulting mixture was stirred at 60° C. for 1 h, cooled to rt. Treated with 200 ml of EtOAc, the mixture was washed with H2O (40 ml), 1N NaOH (3×30 ml), brine (30 ml) and dried (Na2SO4). Removal of the solvent under reduced pressure gave a slightly dark solid. Recrystalization of the solid in hexanes/DCM/EtOAc yielded 3.25 g (85%) of product as a yellow solid: 1H-NMR (CDCl3; 400 MHz) δ 8.20 (d, 1H, J=1.9 Hz), 7.45 (dd, 1H, J=8.9, 1.9 Hz), 6.67 (d, 1H, J=8.9 Hz), 6.29 (br s, 2H), 3.90 (s, 3H). Mass spectrum (ESI, m/z): Calcd. for C9H8N2O2, 177.1 (M+H), found 177.2.

Provenance & Evidence