Hydrochloric Acid → HCID 131730411, compound

Participants

Reaction Steps

2-(3,5-Dichlorophenyl)-1-(methoxycarbonyl)piperidine-4-carboxylic acid (4.6 g, 13.85 mmol) (reference compound 24) was dissolved in methyl THF (69.2 mL) and di(1H-imidazol-1-yl)methanone (3.37 g, 20.77 mmol) added. The suspension was stirred at room temperature overnight under nitrogen (flask 1). In a separate flask potassium 3-ethoxy-3-oxopropanoate (4.24 g, 24.93 mmol) was suspended in methyl THF (69.2 mL) and magnesium chloride (2.373 g, 24.93 mmol) added. The suspension was stirred at 50° C. overnight under nitrogen (flask 2). The white suspension in flask 2 was then added to the brown suspension in flask 1. The resulting suspension was stirred at room temperature for 40 h. The mixture was acidified to pH 1 with 3 M HCl. Water and methyl THF were added. The phases were separated, the organic layer washed with water, satd NaHCO3, brine, dried over MgSO4, filtered and evaporated. Purified by flash chromatography using 20% EtOAc in heptane ->50% EtOAc over 10 CV, 3 CV at 50%. Trans-methyl 2-(3,5-dichlorophenyl)-4-(3-ethoxy-3-oxopropanoyl)piperidine-1-carboxylate (0.6 g, 11%) and cis-methyl 2-(3,5-dichlorophenyl)-4-(3-ethoxy-3-oxopropanoyl)piperidine-1-carboxylate (3.57 g, 64%) were isolated. Cis-isomer: 1H NMR (400 MHz, cdcl3) δ 1.22-1.32 (m, 3H), 1.79-1.94 (m, 2H), 2.03-2.17 (m, 1H), 2.20-2.29 (m, 1H), 2.82-2.93 (m, 1H), 3.24-3.34 (m, 1H), 3.46 (d, 2H), 3.64-3.68 (m, 3H), 4.10-4.23 (m, 3H), 4.83-4.92 (m, 1H), 7.06-7.09 (m, 2H), 7.22-7.25 (m, 1H). MS m/z 402 (M+H)+. Trans-isomer: MS m/z 402 (M+H)+

Provenance & Evidence