Formaldehyde → HCID 86618148, compound

Participants

Reaction Steps

A sample of benzyl (S)-1-((1S,2R,4R)-2-acetamido-4-(4-methoxybenzylamino)cyclohexyl)-2-oxopyrrolidin-3-ylcarbamate (54.45 g, 107 mmol) was dissolved in dichloromethane (400 mL). The resultant solution was cooled to 0° C. under N2 stream and then charged sequentially with triethylamine (29.8 mL, 214 mmol), aqueous formaldehyde (11.96 mL of a 37% solution, 161 mmol), and sodium triacetoxyborohydride (34.0 g, 161 mmol). The ice bath was removed and the reaction was stirred at RT for 2 h before being diluted with 750 mL EtOAc and washed with sat. NaHCO3 (2×250 mL). The organic phase was concentrated in vacuo and the resultant residue was dissolved in EtOAc (750 mL). The organic phase was washed with acid [2×(200 mL 1N HCl/300 mL H2O)]. The acidic washes were combined and then basified with 6N NaOH (80 mL) and sat. NaHCO3 (70 mL). The mixture was extracted with EtOAc (3×500 mL). The organic extracts were combined, washed with brine (1×100 mL), dried (MgSO4), filtered, and concentrated in vacuo. The residue was dissolved in methylene chloride and concentrated; this was repeated twice to afford benzyl (S)-1-((1S,2R,4R)-2-acetamido-4-((4-methoxybenzyl)(methyl)amino)cyclohexyl)-2-oxopyrrolidin-3-ylcarbamate (54.14 g, 104 mmol, 97% yield) as a hard white microcrystalline foam after pumping on high vacuum. LC/MS found [M+H]+=523.6.

Provenance & Evidence