Diisopropylethylamine → [2-[8,9-Dioxo-2,6-diazabicyclo[5.2.0]non-1 (7)-en-2-yl]ethyl]-phosphonic acid bis[1-(benzoyloxy)ethyl]ester

Participants

Reaction Conditions

Reaction Steps

A solution of the starting [2-(8,9-dioxo-2,6-diazabicyclo[5.2.0]non-1(7)-en-2-yl)ethyl]phosphonic acid (19.22 mmol, 5 g) in dry DMF (100 mL) was treated with N,N-diisopropylethylamine (76.88 mmol, 13.39 mL). The reaction mixture was stirred for 30 minutes at ambient temperature after which benzoic acid-1-chloroethyl ester (57.66 mmole, 10.65 g, synthesis described below) was added. The mixture was then stirred at 70° C. for 36 hours, cooled to ambient temperature and diluted with citric acid (2% aqueous solution, 70 mL). The product was extracted with ethyl acetate (3×50 mL), washed with sodium bicarbonate (3%) and brine. The organic layer was dried over magnesium sulfate, filtered, and evaporated to dryness. The residue was flash chromatographed on silica gel. Elution with a gradient of 2 to 8% methanol in chloroform afforded 1.66 g (15.5%) of a stereoisomer of [2-[8,9-Dioxo-2,6-diazabicyclo[5.2.0]non-1(7)-en-2-yl]ethyl]-phosphonic acid bis[1-(benzoyloxy)ethyl]ester (example 8) [MS (ES+): m/e 557 (M+H)] and 0.73 g (6.8%) of a less polar diastereoisomer of [2-[8,9-Dioxo-2,6-diazabicyclo[5.2.0]non-1(7)-en-2-yl]ethyl]-phosphonic acid bis[1-(benzoyloxy)ethyl]ester (example 9) [MS (ES+): m/e 557 (M+H)].

Provenance & Evidence