Concise Synthesis of Key Intermediates of Pyriftalid and Paquinimod via Hydrogenation Method

An efficient and scalable synthesis of 7-amino-3-methylisobenzofuran-1(3H)-one (1) and 2-amino-6-ethylbenzoic acid (2) has been developed via a one-step catalytic hydrogenation. The triethylammonium salt of 2-acetyl-6-nitrobenzoic acid was used as the starting material and 1 was prepared in a biphasic solvent system of toluene/H2O, while 2 was obtained when the solvent was replaced with H2O. Intermediates 1 and 2 could be used to synthesize Pyriftalid and Paquinimod, respectively.