Triethylamine → HCID 86618147, compound

Participants

Reaction Steps

A sample of benzyl (S)-1-((1S,2R,4R)-2-acetamido-4-aminocyclohexyl)-2-oxopyrrolidin-3-ylcarbamate (34.8 g, ca. 90 mmol) was dissolved in methanol (400 ml). The flask was purged with nitrogen and charged with triethylamine (15.61 ml, 112 mmol), followed by 4-methoxybenzaldehyde (13.62 ml, 112 mmol). The reaction was stirred at RT for 14 h, at which time LC/MS of reaction showed complete consumption of primary amine and formation of desired imine (LC/MS found [M+H]+=507.4). The reaction was cooled to 0° C. and charged with sodium borohydride (5.08 g, 134 mmol) in portions over 1 minute. The ice bath was removed after 30 min and the solution stirred for an additional 3.5 h. The reaction was concentrated in vacuo to give a white solid/gum, which was dissolved in 400 mL sat. NaHCO3 and 1200 mL EtOAc. The phases were mixed vigorously and then separated. The organic phase was washed 2×800 mL 0.5N HCl (note: a small third, oily phase was on the bottom in the first extraction; took along with the acid phase). The acid washes were combined, basified with solid NaOH to pH 13, cooled to RT, and then extracted with EtOAc (1×1000 mL; 2×600 mL). The organic extracts were combined, washed with brine (1×120 mL), dried (MgSO4), filtered, and concentrated in vacuo. The residue was dissolved in dichlormethane and concentrated; this procedure was repeated to give benzyl (S)-1-((1S,2R,4R)-2-acetamido-4-(4-methoxybenzylamino)cyclohexyl)-2-oxopyrrolidin-3-ylcarbamate (43.68 g, 86 mmol, 96% yield) as a flowing microcrystalline solid after pumping on high vacuum. LC/MS found [M+H]+=509.6.

Provenance & Evidence