反应详情

To a mixture of 300 mg of 18 (1.06 mmol), 244 mg (1.06 mmol) of 6-(Boc-amino)-caproic acid (Bachem), and 485 mg (1.27 mmol, 1.2 equiv.) of HATU in 4 mL of DMF was added 525 μL (3.0 mmol, ˜3 equiv.) of diisopropylethylamine. The resulting mixture was stirred at room temperature overnight, then diluted with ˜100 mL EtOAc and washed with 1 N HCl (three times), 1 N NaOH (twice), then brine, and dried (MgSO4), filtered, and concentrated to an orange oil. This was dissolved in CH2Cl2, loaded onto silica, and eluted with 3:2 CH2Cl2/CH3CN to give 308 mg (0.62 mmol, 58%) of 19 as a foamy white solid. 1H-NMR (400 MHz, CDCl3, 6 ppm) 7.90 (dd, J=1 Hz, 8 Hz, 2H), 7.60 (tt, J=1 Hz, 8 Hz, 1H), 7.53 (tt, J=1 Hz, 8 Hz, 2H), 5.71 (d, J=6 Hz, 1H), 4.58 (br s, 1H), 4.53 (t, J=8Hz, 1H), 4.47 (m, 1H), 3.66 (s, 3H), 3.54 (q, J=5 Hz, 1H), 3.39 (dd, J=3 Hz, 11 Hz, 1H), 3.08 (m, 2H), 2.24 (m, 2H), 2.02 (t, J=8 Hz, 2H), 1.56 (m, 2H), 1.45 (m, 2H), 1.41 (s, 9H), 1.28 (m, 2H); 13C-NMR (400 MHz, CDCl3, 8 ppm) 173.21, 172.19, 164.53, 138.83, 133.62, 129.58, 128.04, 123.12, 59.13, 53.70, 52.97, 49.68, 40.68, 37.47, 36.59, 30.08, 28.82, 26.64, 25.38; m/z: 498 (M+1)+.

1. washwashed with 1 N HCl (three times), 1 N NaOH (twice), then brine
2. dry with materialdried (MgSO4)
3. filtrationfiltered
4. concentrationconcentrated to an orange oil
5. dissolutionThis was dissolved in CH2Cl2
6. washeluted with 3:2 CH2Cl2/CH3CN