反应详情

Potassium tert-butoxide solution in tetrahydrofuran (1.0 M, 645 μL, 0.645 mmol) was added dropwise to a cooled (0° C.) solution of 2,5-anhydro-3-deoxy-4-O-(5,8-dichloro-1-oxo-1,2,3,4-tetrahydroisoquinolin-7-yl)-1-O-(4-nitrobenzoyl)-L-threo-pentitol (296n, 120 mg, 0.249 mmol) in anhydrous N,N-dimethylformamide (4 mL). After stirring for 30 minutes, a solution of 2-(benzyloxy)-3-(chloromethyl)-4,6-dimethylpyridine (compound Z, 71 mg, 0.273 mmol) in anhydrous N,N-dimethylformamide (1 mL) was added and stirring continued at 0° C. for 30 more minutes. The reaction mixture was diluted with ethyl acetate (50 mL), washed with water (2×50 mL) and brine (50 mL), dried over sodium sulfate, concentrated to dryness, and purified by silica gel chromatography (eluting with a gradient of 0-100% ethyl acetate in heptane), affording 1,4-anhydro-2-O-(2-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-5,8-dichloro-1-oxo-1,2,3,4-tetrahydroisoquinolin-7-yl)-3-deoxy-L-threo-pentitol (296o, 36 mg, 26% yield) as a solid. 1H NMR (400 MHz, CDCl3) δ 7.45 (d, J=7.21 Hz, 2H), 7.29-7.40 (m, 3H), 6.94 (s, 1H), 6.62 (s, 1H), 5.43 (s, 2H), 4.92 (br. s., 1H), 4.87 (s, 2H), 4.15-4.26 (m, 2H), 3.91 (dd, J=10.39, 3.91 Hz, 1H), 3.75-3.84 (m, 1H), 3.66-3.75 (m, 1H), 3.25 (t, J=6.05 Hz, 2H), 2.69 (t, J=6.05 Hz, 2H), 2.42 (s, 3H), 2.34-2.40 (m, 1H), 2.32 (s, 3H), 2.03-2.16 (m, 2H). MS: 557 [M+1].

1. stirringstirring
2. customcontinued at 0° C. for 30 more minutes
3. washwashed with water (2×50 mL) and brine (50 mL)
4. dry with materialdried over sodium sulfate
5. concentrationconcentrated to dryness
6. custompurified by silica gel chromatography (
7. washeluting with a gradient of 0-100% ethyl acetate in heptane),