1,1'-Carbonyldiimidazole → HCID 66732608, compound

Participants

Reaction Steps

1-(Benzyloxycarbonyl)-2-(2-methyl-2H-tetrazol-5-yl)piperidine-4-carboxylic acid (0.828 g, 2.40 mmol) (reference compound 36) was dissolved in THF (7 mL) and then di(1H-imidazol-1-yl)methanone (0.583 g, 3.60 mmol) was added. The reaction was stirred overnight at room temperature (flask 1). In a separate flask potassium 3-ethoxy-3-oxopropanoate (0.816 g, 4.80 mmol) and anhydrous magnesium chloride (0.457 g, 4.80 mmol) were suspended in THF (7.00 mL) and stirred at 50° C. under nitrogen overnight and then allowed to cool to room temperature (flask 2). The content 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. Benzyl 4-(3-ethoxy-3-oxopropanoyl)-2-(2-methyl-2H-tetrazol-5-yl)piperidine-1-carboxylate (499 mg, 59%) was isolated. 1H NMR (400 MHz, cdcl3) δ 1.22-1.31 (m, 3H), 1.72-1.83 (m, 1H), 2.00-2.08 (m, 1H), 2.41 (dt, 1H), 2.70-2.78 (m, 1H), 2.88-2.95 (m, 1H), 3.35-3.63 (m, 3H), 3.99-4.07 (m, 1H), 4.12-4.20 (m, 2H), 4.28 (s, 3H), 5.11-5.21 (m, 2H), 5.59 (t, 1H), 7.27-7.40 (m, 5H). MS m/z 416 (M+H)+

Provenance & Evidence