Benzaldehyde → HCID 16777615, compound

Participants

Reaction Steps

4-Aminopiperidine (4.01 g, 40 mmol) and benzaldehyde (4.251 g, 40 mmol) were dissolved in toluene (70 mL) and refluxed on a Dean-Stark trap until water ceased to evolve. The solvent was evaporated and the residue was reconstituted in dry THF (75 mL). Triethylamine (4.04 g, 40 mmol) was added and the reaction was cooled in an ice bath. With vigorous stirring, propionyl chloride (3.70 g, 40 mmol) was added and the reaction continued for 1.5 hours at rt. The reaction was filtered, and the filtrate was evaporated and treated with 1N HCl (50 mL) for 1 hour. The aqueous phase was washed with Et2O (3×50 mL), basified to pH>10 with NaOH, saturated with sodium chloride and extracted with DCM (5×75 mL). The combined DCM extract was evaporated and azeotropically dried with toluene to give intermediate 1 (4.74 g, 64%) as a light brown oil: 1H NMR (500 MHz, DMSO-d6) δ 4.18 (d, J=11.8 Hz, 1H), 3.74 (d, J=11.8 Hz, 1H), 3.00 (dd, J=11.8, 11.8 Hz, 1H), 2.89 (brs, 2H), 2.82-2.15 (m, 1H), 2.67 (dd, J=11.8 Hz, 11.8 Hz, 1H), 2.28 (q, J=7.1 Hz, 2H), 1.72 (d, J=11.8 Hz, 1H), 1.67 (d, J=11.8 Hz, 1H), 1.14 (q, J=10.2 Hz, 1H), 1.04 (q, J=10.2 Hz, 1H), 0.98 (t, J=7.1 Hz, 3H).

Provenance & Evidence