反应详情

To a solution of Boc-Gly-Ala-Gly prepared as in Example 34B (11.0 g, 36.5 mmol) in anhydrous DMF (270 ml), was added HOBT.circle-solid.H2O (5.46 g, 40.4 mmol), EDC.circle-solid.HCl (7.74 g, 40.4 mmol), and DAla-Gly-OBzl .circle-solid.HCl prepared as in Example 34A (9.95 g, 36.5 mmol). The pH of the resulting solution was adjusted to ~8 (measured by spotting the reaction mixture on moistened Hydrion paper) and the reaction mixture was allowed to stir at room temperature for 12 h thereafter. The solution was concentrated in vacuo and the residue was dissolved in water (50 ml). This solution was extracted with ethyl acetate (3×100 ml). The combined ethyl acetate layers were washed with 1N sodium bisulfate (50 ml), saturated sodium bicarbonate (50 ml) and brine (50 ml). The ethyl acetate solution was dried (magnesium sulfate), filtered and allowed to sit for 12 h undisturbed. Collection of the crystals by filtration and drying at high vacuum afforded 13.4 g (70% yield) of pure product: 1H NMR (DMSO-d6) δ 1.22 (d, J=7.2 Hz, 3H), 1.23 (d, J=7.2 Hz, 3H), 1.38 (s, 9H), 3.58 (d, J=6.0 Hz, 2H), 3.73 (d, J=4.8 Hz, 2H), 3.91 (dd, J =6.0, 3.0 Hz, 2H), 4.32 (m, 2H), 5.14 (s, 2H), 6.91 (t, J=4.8 Hz, 1H), 7.38 (s, 5H), 7.97 (d, J=8.1 Hz, 1H), 8.02 (d, J=6.9 Hz, 1H), 8.19 (t, J=5.4 Hz, 1H), 8.33 (t, J=5.4 Hz, 1H).

1. concentrationThe solution was concentrated in vacuo
2. dissolutionthe residue was dissolved in water (50 ml)
3. extractionThis solution was extracted with ethyl acetate (3×100 ml)
4. washThe combined ethyl acetate layers were washed with 1N sodium bisulfate (50 ml), saturated sodium bicarbonate (50 ml) and brine (50 ml)
5. dry with materialThe ethyl acetate solution was dried (magnesium sulfate)
6. filtrationfiltered
7. waitto sit for 12 h
8. customCollection of the crystals
9. filtrationby filtration
10. customdrying at high vacuum