反应详情

温度

0 °C

Benzyl 3-hydroxyphenylacetate 0.88 g (3.60 mmol) was added to 30 mL of a dry dichloromethane solution containing 3.60 mmol of benzyl 2-(N-benzyloxycarbonylamino)-4-[chloro(methyl)phosphono]butanoate obtained in the same manner as Example 1. After the solution was cooled to 0° C., 0.51 mL (3.60 mmol) of triethylamine was added and stirred at 0° C. for 15 minutes. Thereafter, the temperature was increased and reaction was carried out at 34° C. for 45 minutes. After the completion of the reaction was confirmed by TLC (EtOAc/hexane=1:1), the reaction mixture was vacuum-concentrated and the residue was dissolved in 30 mL of ethyl acetate and the insoluble salt was removed by filtration. The filtrate was vacuum-concentrated, and the crude product was purified by flash column chromatography on neutral silica gel 60 N using a solvent mixture of ethyl acetate and hexane at 4:3 to obtain benzyl 2-(N-benzyloxycarbonylamino)-4-{[3-(benzyloxycarbonylmethyl)phenyl] (methyl)phosphono}butanoate as a colorless oily substance (0.72 g, yield 31%).

1. customobtained in the same manner as Example 1
2. temperatureThereafter, the temperature was increased
3. customreaction
4. waitwas carried out at 34° C. for 45 minutes
5. concentrationthe reaction mixture was vacuum-concentrated
6. dissolutionthe residue was dissolved in 30 mL of ethyl acetate
7. customthe insoluble salt was removed by filtration
8. concentrationThe filtrate was vacuum-concentrated
9. customthe crude product was purified by flash column chromatography on neutral silica gel 60 N
10. additiona solvent mixture of ethyl acetate and hexane at 4:3