Crude 3,4-dihydroisoquinoline hydrochloride 12 (6.48 g) was suspended in methanol (50 mL) under argon protection and cooled to 0 °C. Sodium borohydride (0.8 g, 21 mmol) was slowly added to this suspension. The reaction mixture was stirred at room temperature for 10 minutes and then concentrated. Subsequently, brine (16 mL) and acetonitrile (30 mL) were added to the concentrate and the mixture was then partitioned between ethyl acetate (30 mL) and water (30 mL). The aqueous layer was extracted twice with a solvent mixture of ethyl acetate-acetonitrile (30 mL, 1:1). The organic layers were combined, washed with brine, dried over anhydrous sodium sulfate and concentrated to give a yellow oil. This oily substance was dissolved in methanol (10 mL), 5% hydrochloric acid solution in methanol (20 mL) was added and concentrated again. The residue was crystallized by the addition of ether, and the solid was collected by filtration and washed with ether to give finally 1-(3,4-dimethoxybenzyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (6-HCl, 4.67 g, 89% yield, after a 3-step reaction) as a white solid with a melting point of 211-215 °C. The 1H NMR (DMSO-d6) data were as follows: δ 2.91 (1H, m), 3.16-3.24 (3H, m), 3.36 (1H, m), 3.56 (1H, m), 3.60 (3H, s), 3.80 (3H, s), 3.85 (6H, s), 4.73 (1H, m), 6.17 (1H, s), 6.58 ( 1H, s), 6.72 (1H, d, J = 8.0 Hz), 6.77-6.79 (2H, m), 9.77 (1H, br s), 10.35 (1H, br s). The 1H NMR (D2O) data were as follows: δ 3.01-3.05 (2H, m), 3.16-3.29 (2H, m), 3.41 (1H, m), 3.53 (1H, m), 3.60 (3H, s), 3.72 (3H, s), 3.83 (6H, s), 4.73 (1H, m), 6.36 (1H, s), 6.73 ( 1H, s), 6.83-6.89 (2H, m), 7.00 (1H, m).
