Reaction Steps
Into a 25 mL round bottom flask was placed N-benzyl-(1R, 3R)-1,2,3,4-tetrahydro-6,8-dimethoxy-1,3-dimethylisoquinoline (288 mg, 0.9 mmol) dissolved in methylene chloride (3 mL). Bromine (156 mg, 1.0 mmol) in methylene chloride (1 mL ) was added to the solution. The mixture was stirred for 3 h at room temperature and then diluted with methylene chloride (20 mL) and washed with H2O (2×5 ml). The organic layer was dried with sodium sulfate and concentrated in vacuo to yield 360 mg of crude material. Separation on MPLC (hexane/ethyl acetate; 9:1, 3% Et3N) gave N-benzyl-(1R, 3R)-5-bromo-1,2,3,4-tetrahydro-6,8-dimethoxy-1,3-dimethylisoquinoline [106] (282 mg, 78%) as light yellow oil; 1H-NMR (CDCl3, 200 MHz): δ7.31 [m, 5H, Ph], 6.4 [s, Ar-H(7)], 3.97 [q, J=6.6 Hz, CHCH3 ], 3.91 [s, OMe] 3.84, [d, J=14.4 Hz, CHcHdPh], 3.76 [s, OMe], 3.52 [ddq, J=11.6, 6.0, and 4.6 Hz, CH2CHCH3 ], 3.19 [d, J=14.4 Hz, CHcHdPH], 2.74 [dd, J=17.7 and 4.6 Hz, CHaHbCHCH3 ], 2.45 [dd, J=17.7 and 11.6 Hz, CHaHbCHCH3 ], 1.35 [d, J=6.0 Hz, CH2CHCH3 ], and 1.31 [d, J=6.6 Hz, CHCH3 ]; 13C-NMR (CDCl3, 200 MHz): δ157.0, 154.4, 140.9, 136.1, 128.3 [2C], 128.0 [2C], 126.3, 122.1, 104.5, 94.3, 56.3, 55.3 [2C], 51.3, 49.4, 45.7, 33.1, and 19.8; LRMS (EI): m/z 374 (M+ -15, 70), 360, 294, 268, 226, 203, 190, 162, 145 (all <5), 91 (100), 65, and 39.
