Carbon Dioxide → HCID 25112455, compound

Participants

Reaction Conditions

Reaction Steps

Triethylamine (1.396 g=1.91 ml, 13.8 mmol) is added to a stirred mixture of (R)-3-amino-azepan-2-one hydrochloride (7) in N,N-dimethylformamide (12 ml) at 18-22° C., then stirring is continued for approx. 1 hour. 1-Hydroxybenzotriazole hydrate (2.113 g, 13.8 mmol) is added at 18-22° C. to the stirred mixture, followed by the solution of (3R,4R)-4-tert-butoxycarbonyl-methyl-amino)-5-(3,4-dichloro-phenyl)-3-hydroxy-pentanoic acid (6) in N,N-dimethyl-formamide. N,N-dimethylformamide (2 ml) is used for rinsing. The mixture is cooled to 0-5° C., then 1,3-dicyclohexylcarbodiimide (2.847 g, 13.8 mmol) is added, followed by N,N-dimethylformamide (1.5 ml), used for rinsing. Stirring at approx. 0-5° C. is continued for approx. 1 hour, then the mixture is warmed to approx. 18-22° C. and stirred at that temperature for approx. 20 hours. The precipitated solids are removed by filtration and the filter cake is rinsed with N,N-dimethylformamide (12 ml). The filtrate is concentrated at a mantle temperature of approx. 60° C. under reduced pressure, until a concentrate of approx. 19.5 g is obtained. The resulting suspension is cooled to approx. 20-25° C., then an aqueous solution of potassium hydrogencarbonate (1.92 g, 19.17 mmol) in water (32 ml) is added over a period of approx. 20 minutes under evolution of carbon dioxide to give a suspension. The precipitated solids are isolated by filtration, rinsed with water (24 ml) and dried in vacuo at approx. 60° C. to constant weight to yield crude [(1R,2R)-1-(3,4-dichloro-benzyl)-2-hydroxy-3-((R)-2-oxo-azepan-3-ylcarbamoyl)-propyl]-methyl-carbamic acid tert-butyl ester (8) (6.019 g, 99.8% of theory based on (R)-2-(tert-butoxycarbonyl-methyl-amino)-3-(3,4-dichloro-phenyl-propionic acid (1).

Provenance & Evidence