反应详情

温度

90 °C

To a stirred solution of 1-[4-(piperidin-1-yl)pyrimidin-2-yl]ethanone (Intermediate 52, 0.6 g, 2.92 mmol) in dimethylcarbonate (10 mL), sodium hydride (0.281 g, 11.7 mmol, 60%) was added portion wise at 0-5° C. over a period of 10 min. The reaction mixture was heated to 90° C. for 4 h. The reaction mixture was quenched by adding ice water. The aqueous layer pH was adjusted to neutral with dilute HCl, the aqueous layer was extracted with ethyl acetate (2×50 mL). The organic layer was dried and concentrated. The crude product was purified by column chromatography (75% ethylacetate & pet ether) to obtain methyl 3-oxo-3-[4-(piperidin-1-yl)pyrimidin-2-yl]propanoate 0.4 g (52%).

1. customThe reaction mixture was quenched
2. additionby adding ice water
3. extractionthe aqueous layer was extracted with ethyl acetate (2×50 mL)
4. customThe organic layer was dried
5. concentrationconcentrated
6. customThe crude product was purified by column chromatography (75% ethylacetate & pet ether)