反应详情

温度

-22 °C

To a solution of the benzoic acid derivative prepared above (0.240 g, 0.885 mmol) and NMM (0.446 g, 4.43 mmol, 0.489 ml) in CH2Cl2 (8.9 ml) at -22° C. under N2 was added IBCF (0.121 g, 0.885 mmol, 0.115 ml), and the reaction stirred at -22° C. for 20 min. The HCL.Val-Pro-Val-C2F5 (0.400 g, 0.885 mmol) was added in several portions, and the reaction was stirred at -22° C. for 0.5 h, followed by 4 h at room temperature. The reaction was diluted with CH2Cl2 (30 ml) and then washed successively with 10% HCl (2×15 ml), sat. NaHCO3 (2×15 ml), brine (1×15 ml), and dried over MgSO4. Solvent removal under vacuum gave an off-white foam which was purified by flash chromatography (silica gel; 25/75, hexane/EtOAc) to give 0.295 g (50%) of the title compound as a white solid. TLC: Rf 0.49 (EtOAc). 1H NMR: δ 8.02-7.93 (m, 2H, aryl), 7.85-7.77 (m, 2.25H, aryl and NH), 7.70 (d, J=7.3 Hz, 0.75H, NH), 6.93 (d, J=9.0 Hz, 1H, NH), 5.04-4.96 (m, 1H, α-CH of Val), 4.86 (dd, J=8.7, 6.7 Hz, 1H, α-CH of Val), 4.71 (dd, J=8.1, 2.0 Hz, 0.25H, α-CH of Pro), 4.61 (dd, J=8.1, 3.0 Hz, 0.75H, α-CH of Pro), 3.92-3.64 (m, 6H, CH2OCH2 and CH2N of Pro), 3.07-2.96 (m, 4H, CH2NCH2), 2.55-1.82 (series of m, 6H, 2×β-CH of Val, CH2CH2 of Pro), 1.12-0.85 (m, 12H, 4×CH3). 19F NMR: δ 82.12 (s, CF3, major), -82.16 (s, CF3, minor), -121.50 and -122.74 (AB quartet, J=296 Hz, CF2, minor), -121.56 and -122.60 (AB quartet, J=299 Hz, CF2, major). MS (DCI/CH4): m/z (rel intensity) 669 (MH+, 55), 317 (100). Anal. (C28H37F5N4O7S.0.33H2O): C, H, N: calcd, 8.30; found, 7.82.

1. additionwas added IBCF (0.121 g, 0.885 mmol, 0.115 ml)
2. stirringthe reaction was stirred at -22° C. for 0.5 h
3. waitfollowed by 4 h at room temperature
4. washwashed successively with 10% HCl (2×15 ml), sat. NaHCO3 (2×15 ml), brine (1×15 ml)
5. dry with materialdried over MgSO4
6. customSolvent removal under vacuum
7. customgave an off-white foam which
8. customwas purified by flash chromatography (silica gel; 25/75, hexane/EtOAc)