反应详情

To a solution of 0.214 g (1.55 mmol) of p-nitroaniline and 0.50 g (1.55 mmol) of N-(t-butyloxycarbonyl)-L-aspartic acid 4-benzyl ester (111) in 10 mL of dichloromethane at 25° C. under argon, was added a solution of 0.383 g (1.86 mmol) of DCC in 20 mL of dichloromethane via cannula. The reaction mixture was stirred for 24 h, filtered, concentrated, and column chromatographed on silica gel using a mixture of hexane, methanol, and dichloromethane (40:4:1) as eluant to give 0.45 g of the amide (85% yield; based on reacted p-nitroaniline) and 0.05 g (23% recovery) of p-nitroaniline. Mp 47-50° C.; [α]20D=−36.5° (c 1.3, CHCl3); 1H NMR δ 9.18 (s, 1H, NH), 8.20 (d, J=7 Hz, 2H, Ar), 7.66 (d, J=7 Hz, 2H, Ar), 7.36 (s, 5H, Ar), 5.86 (s, 1H, NH), 5.20 (d, J=12.4 Hz, 1H, OCH2), 5.16 (d, J=12.4 Hz, 1H, OCH2), 4.67 (m, 1H, CHN), 3.09 (dd, J=17, 4 Hz, 1H, CH2CO), 2.82 (dd, J=17, 6 Hz, 1H, CH2CO), 1.49 (s, 9H, t-Bu); 13C NMR δ, 171.6, 169.4, 153.1, 143.4, 135.2, 128.6, 128.5, 128.47, 128.2, 125.0, 119.2, 67.1, 65.8, 51.6, 35.4, 28.2. A solution of 0.15 g (0.34 mmol) of the above amide and 0.85 mL (3.39 mmol) of 4 M HCl in dioxane was stirred at 25° C. for 2 h, neutralized with 10 mL of aqueous NaHCO3, and extracted three times with dichloromethane. The combined organic layer was washed with brine, dried (MgSO4), and concentrated to give 0.122 g of 110 (100% yield): [α]22D=−19° (c, 0.15, CHCl3; 1H NMR δ 10.00 (s, 1H, CONH), 8.22 (d, J=7 Hz, 2H, Ar), 7.75 (d, J=7 Hz, 2H, Ar), 7.34 (s, 5H, Ar), 5.18 (d, J=12.4 Hz 1H, OCH2), 5.14 (d, J=12.4 Hz, 1H, OCH2), 3.83 (dd, J=6.8, 4.4 Hz, 1H, CHN), 3.02 (dd, J=17, 4.4 Hz, 1H, CH2), 2.96 (dd, J=17, 6.8 Hz, 1H, CH2); 13C NMR δ, 174.4, 172.0, 143.4, 135.1, 128.7, 128.5, 128.4, 128.3, 125.1, 118.9, 66.9, 52.4, 38.9. HRMS calcd for C17H18N3O5 (M+1) 344.1169, found 344.1150.

1. filtrationfiltered
2. concentrationconcentrated
3. customcolumn chromatographed on silica gel using
4. additiona mixture of hexane, methanol, and dichloromethane (40:4:1) as eluant