反应详情

N-{[4-((2R,3R)-1-(4-Fluorophenyl)-3-{[2-(4-methoxyphenyl)-2-oxoethyl]thio}-4-oxoazetidin-2-yl)phenoxy]acetyl}glycine (0.04 g, 0.072 mmol) and N-methylmorpholine (0.022 g, 0.217 mmol) were dissolved in CH2Cl2 (4 ml). tert-Butyl D-alaninate hydrochloride (0.016 g, 0.087 mmol) and TBTU (0.030 g, 0.094 mmol) were added. After 2 h, the reaction mixture was purified on silica gel and eluted with EtOAc/CH2Cl2 (25/75). Pure fractions were collected and concentrated. The residue was dissolved in CH2Cl2 (3 ml) and TFA (2 ml). The hydrolysis was completed after 2 h. The reaction mixture was concentrated and MeOH (3 ml) and NABH4 (0.011 g, 0.290 mmol) were added. The mixture was stirred for 5 minutes. The reaction was quenched by the addition of 0.1M NH4OAc buffer (2 ml) and the solvent evaporated. The residue was purified by preparative HPLC using an eluent of 0-50% CH3CN in 0.1M NH4OAc buffer. Freeze-drying of the pure fractions afforded the title compound (0.030 g, 66%) as a colourless solid. M/z: 624.2, (M−1). 1H NMR [(CD3)2SO), 400 MHz] δ 1.16 (d, 3H), 2.83-2.93 (m, 2H), 3.68-3.74 (m, 5H), 3.88-3.95 (m, 1H), 4.23-4.26 (m, 1H), 4.51 (s, 2H), 4.60-4.70 (m, 1H), 5.00-5.03 (m, 1H), 6.81-7.37 (m, 12H), 7.74-7.79 (m, 1H), 8.29-8.34 (m, 1H).

1. customthe reaction mixture was purified on silica gel
2. washeluted with EtOAc/CH2Cl2 (25/75)
3. customPure fractions were collected
4. concentrationconcentrated
5. dissolutionThe residue was dissolved in CH2Cl2 (3 ml)
6. waitThe hydrolysis was completed after 2 h
7. concentrationThe reaction mixture was concentrated
8. additionMeOH (3 ml) and NABH4 (0.011 g, 0.290 mmol) were added
9. customThe reaction was quenched by the addition of 0.1M NH4OAc buffer (2 ml)
10. customthe solvent evaporated
11. customThe residue was purified by preparative HPLC
12. customFreeze-drying of the pure fractions