反应详情

To a solution of 5-benzyloxy-6-(3-chlorobenzylcarbamoyl)-1-(2,2-dimethoxyethyl)-4-oxo-1,4-dihydropyridine-3-carboxylic acid (1 g) obtained in Example 161, Step 4 in tetrahydrofuran (15 ml)-toluene (15 ml) were added triethylamine (0.61 ml) and diphenylphosphoryl azide (0.47 ml) and the mixture was stirred at room temperature for 30 min. The solvent was evaporated, and the residue was dissolved in tetrahydrofuran (8 ml). Triethylamine (0.61 ml) and diphenylphosphoryl azide (0.47 ml) were added again and 2 hr later, and 3 hr later, triethylamine (1.22 ml, 0.61 ml) and diphenylphosphoryl azide (0.94 ml, 0.47 ml) were respectively added, and stirring was continued. After confirmation of disappearance of the starting material, 9-fluorenylmethanol (7.7 g) and toluene (10 ml) were added, and the mixture was stirred under reflux with heating. After 20 min, triethylamine (2.5 ml) was added, and stirring was continued with heating for 1.5 hr. The mixture was concentrated, water was added to the residue and the mixture was extracted twice with ethyl acetate. The combined ethyl acetate layer was washed with brine, dried and concentrated. The residue was subjected to silica gel column chromatography (ethyl acetate:hexane=1:1-chloroform:methanol=15:1) to give 5-amino-3-benzyloxy-1-(2,2-dimethoxyethyl)-4-oxo-1,4-dihydropyridine-2-carboxylic acid 3-chlorobenzylamide (886 mg).

1. customThe solvent was evaporated
2. dissolutionthe residue was dissolved in tetrahydrofuran (8 ml)
3. additionTriethylamine (0.61 ml) and diphenylphosphoryl azide (0.47 ml) were added again and 2 hr later
4. addition3 hr later, triethylamine (1.22 ml, 0.61 ml) and diphenylphosphoryl azide (0.94 ml, 0.47 ml) were respectively added
5. stirringstirring
6. additionAfter confirmation of disappearance of the starting material, 9-fluorenylmethanol (7.7 g) and toluene (10 ml) were added
7. stirringthe mixture was stirred
8. temperatureunder reflux
9. temperaturewith heating
10. waitAfter 20 min
11. additiontriethylamine (2.5 ml) was added
12. stirringstirring
13. temperaturewith heating for 1.5 hr
14. concentrationThe mixture was concentrated
15. additionwater was added to the residue
16. extractionthe mixture was extracted twice with ethyl acetate
17. washThe combined ethyl acetate layer was washed with brine
18. customdried
19. concentrationconcentrated