反应详情

A mixture of zinc dust (6.0 g, 91.7 mmol), 2,2-dimethyl-3,4-dihydro-2H-benzo[h]chromene-5,6-dione (6.0 g, 24.8 mmol), Na2S2O4 (17.26 g, 99.1 mmol), N-(tert-butoxycarbonyl)glycine (8.77 g, 49.6 mmol), triethylamine (3.1 ml, 22.3 mmol), HBTU (18.79 g, 49.6 mmol), and DMF (100 ml) is stirred for 16 hours at room temperature. To the reaction mixture is then added ethyl acetate (300 ml). The reaction is filtered and the filtrate washed with H2O (4×200 ml). The organic extract is dried with Na2SO4, and concentrated under reduced pressure to yield a residue. The residue is dissolved in acetic anhydride (30 ml), zinc dust (3.0 g, 45.9 mmol) and triethylamine (3.35 ml, 24.0 mmol) are then added. The mixture is heated to 90° C. with vigorous stirring and held at 90° C. for 2 hours, after which it is allowed to cool and the solvent is removed under reduced pressure to yield a second residue. The second residue is dissolved in ethyl acetate (200 ml) and washed with water (2×100 ml). The organic extract is dried with Na2SO4 and concentrated under reduced pressure to yield unrefined product. The unrefined product is purified by flash column chromatography on silica, eluting with 2% ethyl acetate in dichloromethane, to afford product about 60% pure. The product is further purified by crystallization from ethyl acetate/hexane, which gives the desired product as pure white solid (3.2 g, 31%). M.p.=177° C.; 400 MHz 1H NMR (CDCl3) δ: 8.21 (d, J=8.4 Hz, 1H), 7.67 (d, J=8.4 Hz, 1H), 7.46 (m, 2H), 5.13 (br. s, 1H), 4.30 (d, J=5.6 Hz, 2H), 2.68 (t, J=6.6 Hz, 2H), 2.38 (s, 3H), 1.87 (t, J=6.6 Hz, 2H), 1.48 (s, 9H), 1.42 (s, 6H); LCMS: 444 [M+H]; Calc. for C24H29NO7: C, 64.94; H, 6.59; N, 3.16; Found C, 64.98; H, 6.51; N, 3.15.

1. filtrationThe reaction is filtered
2. washthe filtrate washed with H2O (4×200 ml)
3. extractionThe organic extract
4. dry with materialis dried with Na2SO4
5. concentrationconcentrated under reduced pressure
6. customto yield a residue
7. temperatureThe mixture is heated to 90° C.
8. stirringwith vigorous stirring
9. waitheld at 90° C. for 2 hours
10. temperatureto cool
11. customthe solvent is removed under reduced pressure
12. customto yield a second residue
13. washwashed with water (2×100 ml)
14. extractionThe organic extract
15. dry with materialis dried with Na2SO4
16. concentrationconcentrated under reduced pressure
17. customto yield unrefined product
18. customThe unrefined product is purified by flash column chromatography on silica
19. washeluting with 2% ethyl acetate in dichloromethane