反应详情

温度

30 °C

4-(4-Benzyloxycarbonylamino-2-fluorophenoxy)pyridine-2-carboxylic acid (500 mg) was dissolved in tert-butyl alcohol (5 ml), and triethylamine (0.457 ml) and diphenylphosphoryl azide (0.310 ml) were added thereto under a nitrogen atmosphere at room temperature, followed by stirring for 1.5 hr. The reaction mixture was heated up to 30° C. and stirred for 1 hr and at 40° C. for 45 min. The reaction mixture was heated up to 50° C. and stirred for 30 min, then heated up to 60° C. and stirred for 30 min. The reaction mixture was heated up to 70° C. and stirred for 30 min and at 80° C. for 30 min. The reaction mixture was heated up to 90° C. and stirred for 1.5 hr, then allowed to cool down to room temperature and stirred for 15 hr. The reaction mixture was partitioned between ethyl acetate (50 ml) and a saturated aqueous solution of sodium hydrogencarbonate (30 ml). The organic layer was washed with water (30 ml) and brine (30 ml) in this order and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, the resultant residue was purified by silica gel column chromatography (Fuji Silysia NH, eluent; heptane:ethyl acetate=3:2). Fractions containing the target compound were concentrated under reduced pressure to give a residue, which was suspended in diethyl ether (3 ml) and hexane (3 ml). The solid was collected by filtration and dried under aeration to provide the titled compound as a pale yellow solid (277 mg, 46.6%).

1. customat room temperature
2. stirringstirred for 1 hr and at 40° C. for 45 min
3. temperatureThe reaction mixture was heated up to 50° C.
4. stirringstirred for 30 min
5. temperatureheated up to 60° C.
6. stirringstirred for 30 min
7. temperatureThe reaction mixture was heated up to 70° C.
8. stirringstirred for 30 min and at 80° C. for 30 min
9. temperatureThe reaction mixture was heated up to 90° C.
10. stirringstirred for 1.5 hr
11. temperatureto cool down to room temperature
12. stirringstirred for 15 hr
13. customThe reaction mixture was partitioned between ethyl acetate (50 ml)
14. washThe organic layer was washed with water (30 ml) and brine (30 ml) in this order
15. dry with materialdried over anhydrous sodium sulfate
16. customThe solvent was removed under reduced pressure
17. customthe resultant residue was purified by silica gel column chromatography (Fuji Silysia NH, eluent; heptane:ethyl acetate=3:2)
18. additionFractions containing the target compound
19. concentrationwere concentrated under reduced pressure
20. customto give a residue, which
21. filtrationThe solid was collected by filtration
22. customdried under aeration