Diphenyl chlorophosphate → 4-nitrobenzyl (4R,5S,6S)-3-[(2S,4S)-2-(2-fluoroethyloxymethyl)-1-(4-nitrobenzyloxycarbonyl)pyrrolidin-4-yl]thio-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate

Participants

Reaction Steps

To a solution of 4-nitrobenzyl (4R)-2-diazo-4-[(2R,3S)-3-{(1R)-1-hydroxyethyl}-4-oxoazetidin-2-yl]-3-oxopentanoate (0.95 g) in dichloroethane (20 ml) was added rhodium(II) acetate (10 mg) under refluxing in a nitrogen stream. After refluxing for 1 hour, the mixture was concentrated under reduced pressure to give a residue. The residue was dissolved in anhydrous acetonitrile (20 ml). To the mixture were added diphenyl chlorophosphate (0.52 ml) and N,N-diisopropyl-N-ethylamine (0.51 ml) at -10°~-5° C. in a nitrogen stream. The mixture was stirred at the same condition for 1 hour. To the mixture were added N,N-diisopropyl-N-ethylamine (0.51 ml) and a solution of (2S,4S)-2-(2-fluoroethyloxymethyl)-4-mercapto-1-(4-nitrobenzyloxycarbonyl)pyrrolidine (0.87 g) in acetonitrile (2 ml) successively at -20° C. The mixture was stirred at the same condition for 30 minutes and then at 0°-10° C. for 3 hours. The mixture was poured into a mixture of water (50 ml) and ethyl acetate (50 ml). The organic layer was separated, washed with brine, dried over magnesium sulfate and concentrated under reduced pressure to give a syrup. The syrup was subjected to a column chromatography on silica gel (20 g) and eluted with a mixture of acetone and dichloromethane (5:95 and then, 10:90 V/V) to give 4-nitrobenzyl (4R,5S,6S)-3-[(2S,4S)-2-(2-fluoroethyloxymethyl)-1-(4-nitrobenzyloxycarbonyl)pyrrolidin-4-yl]thio-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate (0.83 g).

Provenance & Evidence