Acetic Acid → Ethyl 10-(benzyl(methyl)amino)-4-oxo-3-((phenylcarbonyl)oxy)-4,6,7,8,9,10-hexahydro-7,10-ethanopyrimido[1,2-a]azepine-2-carboxylate

Participants

Reaction Steps

To a stirred solution of ethyl 10-amino-4-oxo-3-((phenylcarbonyl)oxy)-4,6,7,8,9,10-hexahydro-7,10-ethanopyrimido[1,2-a]azepine-2-carboxylate hydrochloride (12.75 g, 29.4 mmol) in 1,2-dichloroethane (500 mL) was added triethylamine (4.10 mL, 29.4 mmol) and the resulting mixture was stirred for 5 min. Benzaldehyde (5.94 mL, 58.8 mmol), AcOH (1.682 mL, 29.4 mmol) and NaCNBH3 (5.54 g, 88 mmol) were then added and the mixture stirred at room temp for 6 h. Formaldehyde (4.38 mL, 58.8 mmol) was then added to the reaction and the mixture was stirred at room temperature for 16 h. The reaction was quenched with sat. NaHCO3 and extracted with dichloromethane, dried (Na2SO4), filtered and concentrated. The crude product was the recrystallized from ethyl acetate to afford the title compound (11.6 g, 23.13 mmol, 79% yield)as an off-white solid. 1H NMR (500 MHz, CDCl3) δ: 8.20 (2 H, d, J=7.32 Hz), 7.63 (1 H, t, J=7.32 Hz), 7.50 (2 H, t, J=7.78 Hz), 7.39 (2 H, d, J=7.63 Hz), 7.31 (2 H, t, J=7.48 Hz), 7.20-7.23 (1 H, m), 4.28-4.34 (2 H, m), 4.09 (4 H, brs), 2.53 (3 H, s), 2.47 (1 H, brs), 2.32-2.42 (2 H, m), 2.02-2.10 (2 H, m), 1.89-1.99 (2 H, m), 1.66-1.74 (2 H, m), 1.22 (3 H, t, J=7.17 Hz). LCMS (M+H)=502.37.

Provenance & Evidence