反应详情

温度

50 °C

Ethyl potassium malonate (1.065 g, 6.26 mmol) and MgCl2 (0.496 g, 5.21 mmol) were added to dry THF (50 mL). The reaction mixture was stirred vigorously for 4 h at 50° C. (flask 1). 1-(Methoxycarbonyl)-2-(4-(trifluoromethyl)benzyl)piperidine-4-carboxylic acid (1.8 g, 5.21 mmol) (reference compound 47) and carbonyldiimidazole (1.268 g, 7.82 mmol) were added to dry THF (50 ml) at 5° C. (flask 2). The contents of flask 2 was added to flask 1 and the resulting suspension was stirred at room temperature overnight. THF was evaporated and the reaction mixture was partitioned 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 15-85 and ended 40-60. Trans-methyl 4-(3-ethoxy-3-oxopropanoyl)-2-(4-(trifluoromethyl)benzyl)piperidine-1-carboxylate (0.93 g, 42.9%) was isolated. 1H NMR (600 MHz, cdcl3) δ 1.20-1.29 (m, 3H), 1.46-1.99 (m, 4H), 2.74-3.04 (m, 4H), 3.34-3.70 (m, 5H), 4.01-4.32 (m, 3H), 4.60 (d, 1H), 7.22-7.38 (m, 2H), 7.51-7.56 (m, 2H). MS m/z 416 (M+H)+

1. additionThe contents of flask 2 was added to flask 1
2. stirringthe resulting suspension was stirred at room temperature overnight
3. customTHF was evaporated
4. customthe reaction mixture was partitioned between water and diethyl ether
5. customThe organic phase was isolated
6. dry with materialdried with Na2SO4
7. filtrationfiltered through celite
8. customthe solvent was evaporated