反应详情

Ethyl 6-[(5-chloro-2-{[(4-chloro-2-fluorophenyl)methyl]oxy}phenyl)methyl]-2-pyridinecarboxylate (204.7 g) was dissolved in ethanol (1.5 L) and stirred under nitrogen at reflux until all the starting material is in solution. 2M Sodium hydroxide (355 ml) was added and the solution heated under reflux for 1 hr 10 minutes. HPLC showed that there was no residual starting material. The solution was filtered and the filter washed with a ˜1:1 mixture of hot ethanol (515 ml) and water (520 ml). The combined filtrate and wash were re-heated to reflux, and water (1.5 L) was added slowly over 5 minutes. The solution was then cooled to 20+/−5° C. over 2 hours and stirred for 1 hour. The product was then filtered off and washed with ethanol:water (1:1, 1030 ml), then ethanol:water (˜1:3; 385 ml ethanol:1.15 L water). The resulting solid was dried to a constant weight at 60° C. under vacuum, to give the title compound. (186 g).

1. temperatureat reflux until all the starting material
2. temperaturethe solution heated
3. temperatureunder reflux for 1 hr 10 minutes
4. filtrationThe solution was filtered
5. washthe filter washed with a ˜1:1 mixture of hot ethanol (515 ml) and water (520 ml)
6. washThe combined filtrate and wash
7. temperaturewere re-heated
8. temperatureto reflux
9. additionwater (1.5 L) was added slowly over 5 minutes
10. temperatureThe solution was then cooled to 20+/−5° C. over 2 hours
11. stirringstirred for 1 hour
12. filtrationThe product was then filtered off
13. washwashed with ethanol:water (1:1, 1030 ml)
14. customThe resulting solid was dried to a constant weight at 60° C. under vacuum