反应详情

Next, 0.95 g (1.82 mmol) of benzyl 2-(N-benzyloxycarbonylamino)-4-[(4-cyanophenyl)(methyl)phosphono]butanoate and 1.18 g (10.9 mmol) of anisole were dissolved in 10 mL of dry nitromethane and mixed with 0.73 g (5.46 mmol) of aluminum trichloride at room temperature. After stirring was carried out at room temperature for 1 hour, 20 mL of water was added and stirred for 10 minutes. The mixture was washed with 50 mL of an ether three times and a water layer was separated, and methanol was added to adjust the final concentration of methanol to be 30%. The solution was passed through a short column of neutral silica gel 60N to remove aluminum hydroxide. Without being concentrated, the effluent was purified by medium pressure reversed-phase column chromatography ODS-S-50B. The column was eluted with a linear gradient of 30 to 60% methanol at a flow rate of 6 mL/min and the fractions containing the compound eluted at 45% methanol were collected. The elution and purity of the compound were confirmed by TLC (BuOH/AcOH/H2O=5:2:2, ninhydrin coloration). After vacuum concentration, freeze drying was carried out to obtain 2-amino-4-[(4-cyanophenyl)(methyl)phosphono]butanoic acid (0.38 g, yield 70%) as a colorless solid.

1. stirringstirred for 10 minutes
2. washThe mixture was washed with 50 mL of an ether three times
3. customa water layer was separated
4. additionmethanol was added
5. customto remove aluminum hydroxide
6. concentrationWithout being concentrated
7. customthe effluent was purified by medium pressure reversed-phase column chromatography ODS-S-50B
8. washThe column was eluted with a linear gradient of 30 to 60% methanol at a flow rate of 6 mL/min
9. additionthe fractions containing the compound
10. washeluted at 45% methanol
11. customwere collected
12. washThe elution and purity of the compound
13. concentrationAfter vacuum concentration, freeze
14. customdrying