[Synthesis]
General procedure for the synthesis of 3-bromo-5-cyanobenzoic acid from methyl 3-bromo-5-cyanobenzoate: to methyl 3-bromo-5-carbamoylbenzoate (2.8 g, 10.8 mmol, 1.0 equiv) was added phosphorous triclorethane (POCl3, 30 mL) and the reaction mixture was heated at 100 °C overnight. Upon completion of the reaction, phosphorous trichloride was removed by distillation under reduced pressure, water was added to the residue and the aqueous phase was extracted with ethyl acetate (EtOAc). The organic extracts were combined, dried with anhydrous sodium sulfate (Na2SO4), filtered and concentrated under reduced pressure to give the crude product. The crude product was purified by column chromatography (eluent: petroleum ether/ethyl acetate, 20:1) to afford methyl 3-bromo-5-cyanobenzoate (2.5 g, 96% yield). The ester (2.5 g) was dissolved in tetrahydrofuran (THF, 30 mL) and lithium hydroxide monohydrate (LiOH-H2O, 1.7 g, 41.6 mmol, 1.54 equiv) and water (10 mL) were added. The reaction mixture was stirred at room temperature overnight. Upon completion of the reaction, THF was removed by distillation under reduced pressure and the aqueous phase was acidified with dilute hydrochloric acid (HCl) and extracted with ethyl acetate (EtOAc). The organic extracts were combined, dried with anhydrous sodium sulfate (Na2SO4), filtered and concentrated under reduced pressure to give the crude product. The crude product was purified by column chromatography (eluent: dichloromethane/methanol, 50:1) to afford 3-bromo-5-cyanobenzoic acid as a white solid (2 g, 85% yield).LC-MS: m/z 248.0, 249.9 [M + Na]+. 1H NMR (400 MHz, DMSO) δ 13.67 (br s, 1H), 8.40 (s, 1H ), 8.24 (s, 1H), 8.24 (s, 1H). |