反应详情

温度

45 °C

A solution of sodium methoxide (65.8 g, 1.22 mol) in methanol (300 ml) was treated portionwise with diethylacetamidomalonate (132.3 g, 0.61 mol) maintaining a temperature of ca. 45° C. The mixture was then heated under reflux for 15 min. The mixture was cooled to 50° C. then treated slowly with a suspension of 2-chloromethylpyridine hydrochloride (100 g, 0.61 mol), the pink suspension was then heated under reflux for a further 6 h. Water (500 ml) was added followed by 10M sodium hydroxide (122 ml, 1.22 mol) and the pH was maintained at ca. 11 while heating the mixture at 70° C. overnight. The mixture was cooled to RT and the methanol removed in vacuo. The aqueous residue was washed with ethyl acetate (2×500 ml), then acidified to pH 5 and further washed with ethyl acetate (2×500 ml), before evaporating in vacuo to provide a semi-solid. The residue was triturated with hot ethanol (500 ml) and the sodium chloride removed by filtration. The filtrate was then evaporated in vacuo and the residue crystallised from methanol-ethyl acetate to provide the title compound (70 g, 66%) as a yellow solid.

1. temperatureThe mixture was then heated
2. temperatureunder reflux for 15 min
3. temperatureThe mixture was cooled to 50° C.
4. temperaturethe pink suspension was then heated
5. temperatureunder reflux for a further 6 h
6. temperaturethe pH was maintained at ca. 11
7. temperaturewhile heating the mixture at 70° C. overnight
8. temperatureThe mixture was cooled to RT
9. customthe methanol removed in vacuo
10. washThe aqueous residue was washed with ethyl acetate (2×500 ml)
11. washfurther washed with ethyl acetate (2×500 ml)
12. custombefore evaporating in vacuo
13. customto provide a semi-solid
14. customThe residue was triturated with hot ethanol (500 ml)
15. customthe sodium chloride removed by filtration
16. customThe filtrate was then evaporated in vacuo
17. customthe residue crystallised from methanol-ethyl acetate