General procedure for the synthesis of 3-morpholin-4-ylmethylbenzoic acid from methyl 3-(4-morpholinylmethyl)benzoate: to a solution of methyl 3-(4-morpholinylmethyl)benzoate (5.02 g, 21.0 mmol) in methanol (100 mL) was added a sodium hydroxide solution (21.0 mL, 42.0 mmol, 2M). The reaction mixture was heated at 50 °C with stirring for 16 hours. After completion of the reaction, the solvent was removed by distillation under reduced pressure. The residue was adjusted to pH=3 with 1M hydrochloric acid and the resulting suspension was subsequently filtered. The collected solid was dissolved in acetonitrile (15 mL) and concentrated to afford 3-(morpholin-4-ylmethyl)benzoic acid (4.6 g, 100% yield) as a white solid, which was used directly in the subsequent reaction without further purification.
