22171-15-9

154128-83-3

22171-15-9

Preparative Example 1. Synthesis of 4-benzyloxybenzylamine: Potassium phthalimide (20 g, 0.108 mol) was added to a solution of 4-benzyloxybenzyl chloride (25 g, 0.107 mol) in N,N-dimethylformamide (75 mL), and the reaction was stirred for 3 hours. After completion of the reaction, the reaction solution was cooled to room temperature and extracted with ethyl acetate and water by partition. The organic layer was washed with water and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to give 2-(4-benzyloxybenzyl)-isoindole-1,3-dione (37 g, quantitative yield) as a light brown solid. Subsequently, 2-(4-benzyloxybenzyl)-isoindole-1,3-dione (37 g, 0.107 mol) was dissolved in ethanol (1 L), hydrazine monohydrate (8.04 g, 0.161 mol) was added, and stirred at reflux for 8 hours. After completion of the reaction, it was cooled to room temperature, water was added and ethanol was removed by vacuum evaporation. The residue was extracted with ethyl acetate and water by partitioning, and the organic layer was washed sequentially with water, 2N aqueous sodium hydroxide solution and water, and dried with anhydrous magnesium sulfate. The solvent was removed by distillation under reduced pressure and the residue was purified by NH silica gel column chromatography (eluent: hexane/ethyl acetate=2:1, using Fuji Silysia NH silica gel) to afford the title compound 4-benzyloxybenzylamine (15 g, 64% yield) as a white solid.