Reaction Steps
3-Methyl-6-benzyloxy-7-methoxy-1,2,3,4-tetrahydroisoquinoline (338 mg, 1.2 mmol) was dissolved in anhydrous DMF (3.6 mL), DIPEA (314 mg, 2.4 mmol) and 2,5-dimethoxybenzyl chloride (279 mg, 1.5 mmol) were added. The mixture was heated to 80° C. for 20 h, cooled to room temperature and poured into water (50 mL) and ammonium chloride (saturated, 2 mL). The mixture was extracted with ethyl acetate (2×50 mL). The combined organic layers were dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by flash column chromatography using Flashmaster (SiO2: 20 g, hexane 100% to hexane/ethyl acetate 50/50). W8 was obtained as sticky orange oil (395 mg, 76%). 1H NMR (270 MHz, CDCl3) δ 1.14 (3H, d, J 6.3, CHCH3), 2.48 (1H, dd, J 16.3, 6.0, one of ArCH2CH), 2.86 (1H, dd, J 16.1, 4.8, one of ArCH2CH), 3.11 (1H, sext, J 6.1, CHCH3), 3.58-3.77 (4H, m, 2×ArCH2N), 3.76 (3H, s, OCH3), 3.77 (3H, s, OCH3), 3.81 (3H, s, OCH3), 5.11 (2H, s, OCH2Ph), 6.50 (1H, s, CH), 6.61 (1H, s, CH), 6.74 (1H, dd, J 8.8, 3.0, CH), 6.80 (1H, d, J 8.8, CH), 7.07 (1H, d, J 2.8, CH), 7.24-7.47 (5H, m, OCH2C6H5). 13C NMR (67.5 MHz, CDCl3): δ 15.5, 34.5, 50.0, 51.4, 52.4, 55.7, 56.0, 56.0, 71.0, 109.9, 111.3, 111.9, 114.4, 116.0, 125.8, 127.0, 127.2, 127.7, 128.4, 128.9, 137.3, 146.5, 147.7, 151.9, 153.6.
