反应详情

温度

50 °C

To a stirred solution of ethyl 6-(3-chloro-4-fluorobenzyl)-4-hydroxy-5-oxo-5,6,7,8-tetrahydro-2,6-naphthyridine-1-carboxylate (5.0 g; see Example 12, Step 6) and sodium acetate (0.89 g) in acetic acid (90 mL) was added peracetic acid (28 mL). The mixture was then heated at 50° C. overnight. The mixture was cooled to 5° C. and saturated NaHSO4 (17 mL) added, keeping the temperature at less than 25° C. The mixture was concentrated to 50% original volume and partitioned between tert-butyl methyl ether (100 mL) and water (50 mL). The organic phase collected and the volatiles evaporated. The residue was dissolved in toluene (50 mL) and volatiles evaporated, the residue dissolved in toluene (50 mL) and evaporation repeated. Finally the residue was dissolved in toluene (20 mL). Acetic anhydride (3.9 mL) was added and the mixture heated at reflux until complete by HPLC analysis. The mixture cooled to ambient temperature and sodium ethoxide in ethanol (20 mL) was added. The reaction mixture stirred overnight. 2N HCl (31 mL) was added and the title product isolated by filtration.

1. temperatureThe mixture was cooled to 5° C.
2. customat less than 25° C
3. concentrationThe mixture was concentrated to 50% original volume
4. custompartitioned between tert-butyl methyl ether (100 mL) and water (50 mL)
5. customThe organic phase collected
6. customthe volatiles evaporated
7. dissolutionThe residue was dissolved in toluene (50 mL)
8. customvolatiles evaporated
9. dissolutionthe residue dissolved in toluene (50 mL)
10. customevaporation
11. dissolutionFinally the residue was dissolved in toluene (20 mL)
12. additionAcetic anhydride (3.9 mL) was added
13. temperaturethe mixture heated
14. temperatureat reflux until complete by HPLC analysis
15. temperatureThe mixture cooled to ambient temperature
16. additionsodium ethoxide in ethanol (20 mL) was added
17. addition2N HCl (31 mL) was added