Hydrochloric Acid → HCID 66731968, compound

Participants

Reaction Steps

2-(2,4-Dichlorophenyl)-1-(methoxycarbonyl)piperidine-4-carboxylic acid (2.44 g, 7.35 mmol) (reference compound 23) was dissolved in methyl THF (36.7 mL) and di(1H-imidazol-1-yl)methanone (1.787 g, 11.02 mmol) added. The suspension was stirred at room temperature under nitrogen for 6 h (flask 1). In a separate flask potassium 3-ethoxy-3-oxopropanoate (2.250 g, 13.22 mmol) was suspended in methyl THF (36.7 mL) and magnesium chloride (1.259 g, 13.22 mmol) added. The suspension was stirred under nitrogen for 6 h (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 separated. The organic layer was 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, 3CV at 50%. Repurified by flash chromatography using 20% EtOAc in EtOAc ->30% EtOAc over 12 CV. Methyl 2-(2,4-dichlorophenyl)-4-(3-ethoxy-3-oxopropanoyl)piperidine-1-carboxylate (1.55 g, 52%) was isolated.

Provenance & Evidence