Acetic Acid → Benzyl 4-oxo[1,4'-bipiperidine]-1'-carboxylate

Participants

Reaction Steps

Benzyl 4-oxopiperidine-1-carboxylate (29.5 g, 126 mmol), 4,4-dimethoxypiperidine hydrochloride (20 g, 110 mmol), and trietylamine (16.9 mL, 1121 mmol) were stirred in 1,2-dichloroethane (600 mL). Sodium triacetoxyborohydride (30.4, 143 mmol) was added at 0° C. (over 30 minutes) followed by acetic acid (8.2 mL, 143 mmol) and the solution was stirred at room temperature for 24 h. 1N NaOH (100 mL) was added to the mixture and the solution was extracted with dichloromethane (3×100 mL). The combined organic extracts were dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was dissolved in acetone (300 mL) and HCl (50 mL, 5N to 6N in 2-propanol) was added and was heated at reflux overnight. The mixture was concentrated in vacuo, diluted with dichloromethane (100 ml) and extracted with HCl 1N (4×100 ml). The aqueous extracts were combined and basified with NaOH pallets. The solution was then extracted with dichloromethane (3×100 mL), combined organic extracts were dried with anhydrous sodium sulphate, filtered and concentrated in vacuo to afford the titled compound (23 g, 66%) 1H-NMR (300 MHz, CD3OD): δ 7.30 (5H, m), 5.10 (2H, s) 4.21 (2H, d, J=13.5 Hz) 2.87 (4H, t, J=6.2 Hz), 2.77-2.70 (1H, m) 2.62-2.58 (2H, m), 2.40 (2H, t, J=6.2 Hz) 1.86 (2H, d, J=12.0 Hz), 1.75 (2H, t, J=5.6 Hz) 1.42 (2H, m).

Provenance & Evidence