反应详情

温度

45 °C

To a stirred suspension of ethyl 6-(3-chloro-4-fluorobenzyl)-3,4-dihydroxy-5-oxo-5,6,7,8-tetrahydro-2,6-naphthyridine-1-carboxylate (40 g) in DMF (200 mL) was added magnesium methoxide in methanol (100 mL). The mixture heated at 40-50° C. for 3 hours. The excess methanol distilled off, and methyl tosylate (18 mL) was added. The reaction mixture was heated at 50° C. overnight, then cooled to 25° C., and then quenched into 1N HCl (100 mL). The suspension stirred for 1 hour at ambient temperature. The product was isolated by filtration, and the filter cake washed with water (2×100 mL) and then dried on the filter under an atmosphere of nitrogen. The crude product was suspended in methanol (460 mL), heated at reflux temperature for 1 hour, and then allowed to cool to ambient temperature. The product was isolated by filtration and the filter cake washed with cold methanol (2×40 mL) and dried to give the title product.

1. distillationThe excess methanol distilled off
2. additionmethyl tosylate (18 mL) was added
3. temperatureThe reaction mixture was heated at 50° C. overnight
4. temperaturecooled to 25° C.
5. customquenched into 1N HCl (100 mL)
6. customThe product was isolated by filtration
7. washthe filter cake washed with water (2×100 mL)
8. customdried on the
9. filtrationfilter under an atmosphere of nitrogen
10. temperatureheated
11. temperatureat reflux temperature for 1 hour
12. temperatureto cool to ambient temperature
13. customThe product was isolated by filtration
14. washthe filter cake washed with cold methanol (2×40 mL)
15. customdried