The general procedure for the synthesis of methyl 4-cyano-2-methoxybenzoate from methanol and 4-cyano-2-methoxybenzoic acid was as follows: 4-cyano-2-methoxybenzoic acid (1.00 g, 5.648 mmol, Biogene) was dissolved in methanol (15.0 mL), and p-toluenesulfonic acid monohydrate (286 mg, 1.48 mmol, and Aldrich) as a catalyst. The reaction mixture was heated to reflux under argon protection for 16 hours. After completion of the reaction, the solvent was removed by rotary evaporation. The reaction mixture was extracted with ethyl acetate (EtOAc) and washed sequentially with saturated sodium carbonate solution (Na2CO3), water and saturated sodium chloride solution (NaCl). The organic phase was separated, dried with anhydrous sodium sulfate (Na2SO4), filtered and concentrated to give methyl 4-cyano-2-methoxybenzoate (1.04 g, 96.4% yield).
