1,1'-Carbonyldiimidazole → HCID 131730425, compound

Participants

Reaction Conditions

Reaction Steps

Ethyl potassium malonate (1.567 g, 9.21 mmol) and MgCl2 (0.731 g, 7.67 mmol) were added to dry THF (50 mL). The reaction flask was stirred vigorously for 4 h at 50° C. (flask 1). 1-(Methoxycarbonyl)-2-(3-methyl-4-(trifluoromethyl)phenyl)piperidine-4-carboxylic acid (2.65 g, 7.67 mmol) (reference compound 29) and carbonyldiimidazole (1.867 g, 11.51 mmol) were added to dry THF (50 mL) at room temperature (flask 2). The contents of flask 2 was added to flask 1 and the resulting mixture stirred at room temperature 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 0-100 and ended 100-0. Trans-methyl 4-(3-ethoxy-3-oxopropanoyl)-2-(3-methyl-4-(trifluoromethyl)phenyl)-piperidine-1-carboxylate (0.69 g, 22%) and cis-methyl 4-(3-ethoxy-3-oxopropanoyl)-2-(3-methyl-4-(trifluoromethyl)phenyl)piperidine-1-carboxylate (1.40 g, 44%) were isolated. Cis-isomer: 1H NMR (600 MHz, cdcl3) δ 1.25 (t, 3H), 1.00-2.29 (m, 4H), 2.44 (s, 3H), 2.47-2.95 (m, 1H), 3.27-3.34 (m, 1H), 3.37-3.48 (m, 2H), 3.62 (s, 3H), 3.66-4.20 (m, 3H), 4.88-4.96 (m, 1H), 7.05-7.11 (m, 2H), 7.50-7.54 (m, 1H). Trans-isomer: 1H NMR (600 MHz, cdcl3) δ 1.22 (t, 3H), 1.47-2.03 (m, 4H), 2.47 (s, 3H), 2.49-2.89 (m, 2H), 3.40-3.47 (m, 2H), 3.74 (s, 3H), 4.15 (q, 2H), 4.11-4.36 (m, 1H), 5.37-5.75 (m, 1H), 7.06-7.13 (m, 2H), 7.57 (d, 1H).

Provenance & Evidence