反应详情

温度

50 °C

Ethyl potassium malonate (2.414 g, 14.18 mmol) and MgCl2 (1.125 g, 11.82 mmol) were added to dry THF (75 mL). The reaction flask was stirred vigorously for 4 h at 50° C. (flask 1). 1-(Methoxycarbonyl)-2-(4-(methylsulfonyl)benzyl)piperidine-4-carboxylic acid (4.2 g, 11.82 mmol) (reference compound 51) and carbonyldiimidazole (2.87 g, 17.73 mmol) were added to dry THF (75 mL) at room temperature (flask 2). More di(1H-imidazol-1-yl)methanone (0.5 g) was added and after 2 h the contents of flask 2 was added to flask 1 at room temperature and stirred overnight. The reaction mixture was dissolved between water and diethyl ether. The organic phase was isolated, dried with Na2SO4, filtered through celite and the solvent was evaporated. Chromatography using the Biotage equipment. Gradient eluation using ethylacetate-heptane, started 10-90 and ended 100-0. Methyl 4-(3-ethoxy-3-oxopropanoyl)-2-(4-(methylsulfonyl)benzyl)piperidine-1-carboxylate (3.99 g, 79%) was isolated.

1. additionwas added to flask 1 at room temperature
2. stirringstirred overnight
3. customThe organic phase was isolated
4. dry with materialdried with Na2SO4
5. filtrationfiltered through celite
6. customthe solvent was evaporated