1,1'-Carbonyldiimidazole → HCID 131730441, compound

Participants

Reaction Steps

1-(Benzyloxycarbonyl)-2-(1-methyl-1H-tetrazol-5-yl)piperidine-4-carboxylic acid (0.495 g, 1.43 mmol) (reference compound 37) was dissolved in THF (4 mL) and then di(1H-imidazol-1-yl)methanone (0.349 g, 2.15 mmol) was added. The reaction was stirred overnight at room temperature (flask 1). In a separate flask potassium 3-ethoxy-3-oxopropanoate (0.488 g, 2.87 mmol) and anhydrous magnesium chloride (0.273 g, 2.87 mmol) were suspended in THF (4.00 mL) and stirred at 50° C. under nitrogen overnight and then allowed to cool to room temperature (flask 2). The contents of flask 1 was added to flask 2 and stirred under nitrogen over the weekend (72 h). The reaction was quenched by addition of 2 M HCl. The mixture was extracted three times with EtOAc, the combined organic phase was evaporated and purified on a 50 g Biotage column with heptane/EtOAc 88/12-100/0 over 12 CV. Cis-benzyl 4-(3-ethoxy-3-oxopropanoyl)-2-(1-methyl-1H-tetrazol-5-yl)piperidine-1-carboxylate (482 mg, 81%) was isolated. 1H NMR (600 MHz, cdcl3) δ 1.25 (t, 3H), 1.89-1.97 (m, 1H), 2.05-2.12 (m, 1H), 2.28-2.34 (m, 1H), 2.59-2.66 (m, 1H), 2.93 (p, 1H), 3.35-3.41 (m, 1H), 3.62 (dd, 2H), 3.85-3.98 (m, 4H), 4.16 (q, 2H), 5.09 (q, 2H), 5.36-5.42 (m, 1H), 7.21-7.37 (m, 5H). MS m/z 416 (M+H)+

Provenance & Evidence