反应详情

A solution of methyl 2-{[1-(tert-butoxycarbonyl)-4-methylpiperidin-4-yl]carbonyl}-1,2,3,4-tetrahydroisoquinoline-6-carboxylate.[HCl] (0.260 g, 0.737 mmol) in MeOH (8.0 mL) was treated with acetaldehyde (0.414 g, 7.37 mmol) and MgSO4 (excess). The reaction mixture was stirred at rt for 1 h, and sodium cyanoborohydride (93 mg, 1.47 mmol) was added in portions. The resulting mixture was stirred for 3 h at rt and then filtered to remove the MgSO4. The filtrate was washed with water and brine, dried over Na2SO4, filtered and concentrated. The resulting residue was purified by column chromatography (SiO2, 0-20% MeOH in DCM) to give methyl 2-[(1-ethyl-4-methylpiperidin-4-yl)carbonyl]-1,2,3,4-tetrahydroisoquinoline-6-carboxylate (55 mg, 22%). LC-MS: (FA) ES+ 345; 1H NMR (400 MHz, CDCl3) δ 7.86-7.80 (m, 2H), 7.18 (d, J=7.9 Hz, 1H), 4.78 (s, 2H), 3.89 (s, 3H), 3.88-3.83 (m, 2H), 2.91 (t, J=5.5 Hz, 2H), 2.77-2.67 (m, 2H), 2.42 (q, J=7.2 Hz, 2H), 2.36-2.20 (m, 4H), 1.75-1.65 (m, 2H), 1.30 (s, 3H), 1.09 (t, J=7.2 Hz, 3H).

1. stirringThe resulting mixture was stirred for 3 h at rt
2. filtrationfiltered
3. customto remove the MgSO4
4. washThe filtrate was washed with water and brine
5. dry with materialdried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated
8. customThe resulting residue was purified by column chromatography (SiO2, 0-20% MeOH in DCM)