Diisopropylethylamine → HCID 67387290, compound

Participants

Reaction Steps

To a solution of 2-(2-oxo-3,3-diphenylpiperidin-1-yl)acetic acid, obtained in Example 1E (0.95 g, 3.08 mmol) and tert-butyl 4-aminopiperidine-1-carboxylate (CAS 87120-72-7) in dichloromethane (10 mL) was added O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (1.171 g, 3.08 mmol) and diisopropylethylamine (2.6 mL, 13.86 mmol). The reaction mixture was stirred at ambient temperature overnight, then diluted with dichloromethane and washed with 1 N HCl (10 mL), water, 1 N NaOH (10 mL), water, dried over MgSO4, and evaporated to yield tert-butyl 4-(2-(2-oxo-3,3-diphenylpiperidin-1-yl)acetamido)piperidine-1-carboxylate (0.8 g, 60%). To a solution of this product in methanol (10 mL) was added 4 N HCl/dioxane (2 mL), and the reaction mixture was stirred at room temperature for 3 hours. It was concentrated in vacuo and partitioned between 1 N NaOH and dichloromethane. The organic layer was concentrated and chromatographed on an Analogix 15-24 g silica column, eluting with a 2-5% gradient of methanol/dichloromethane to yield the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 7.19-7.35 (m, 10H), 6.99 (d, J=6.4 Hz, 1H), 4.01 (s, 2H), 3.75-3.95 (m, 1H), 3.52 (t, J=6.6 Hz, 2H), 3.04-3.14 (m, 2H), 2.63-2.72 (m, 2H), 2.57-2.64 (m, 2H), 1.77-1.95 (m, 4H), 1.37-1.53 (m, 2H); MS (ESI+) m/z 392 (M+H)+.

Provenance & Evidence