Preparation of Intermediate 1-16: p-Methoxybenzaldehyde (1.8 mL, 14.8 mmol) was mixed with 4-methoxybenzylamine (1.9 mL, 14.8 mmol) in 50 mL of ethanol and the reaction was carried out at reflux for 4 hours. Upon completion of the reaction, the mixture was cooled to 0 °C and sodium borohydride (562 mg, 14.8 mmol) was slowly added followed by stirring at room temperature for 18 hours. After cooling to 0 °C again, 50 mL of water and 250 mL of dichloromethane were added to separate the organic phase. The aqueous layer was further extracted with dichloromethane (2 x 250 mL). All organic layers were combined, dried with anhydrous magnesium sulfate, filtered and concentrated. The residue was dissolved in 100 mL of ether, cooled to 0 °C, and about 10 mL of a dioxane solution of 4N HCl was added slowly and stirred at 0 °C for 2 hours. The resulting white solid was collected by filtration and washed with ether/ethyl acetate to afford the target product bis-(4-methoxybenzyl)-amine hydrochloride (3.99 g, 91% yield). The product was characterized by 1H NMR (300 MHz, DMSO): δ 9.40 (s, 2H), 7.45 (d, J=8.7 Hz, 4H), 6.98 (d, J=8.7 Hz, 4H), 4.03 (s, 4H), 3.77 (s, 6H).
