(R)-4-Nitrobenzyl 2-diazo-4-((2R,3S)-3-((R)-1-hydroxyethyl)-4-oxoazetidin-2-yl)-3-oxopentanoate → 1-Azabicyclo[3.2.0]heptane-2-carboxylic acid, 6-[(1R)-1-hydroxyethyl]-4-methyl-3,7-dioxo-, (4-nitrophenyl)methyl ester, (4R,5R,6S)-

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 (1.00 g) in 1,2-dichloroethane (10 ml) was added rhodium(II) octanoate (10 mg) under refluxing. After refluxing for 30 minutes, the reaction mixture was cooled and evaporated in vacuo to give a residue. The residue was dissolved in benzene (5 ml) and evaporated. This operation was repeated once again and the residue was dried in vacuo to give 4-nitrobenzyl (4R,5R,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-3,7-dioxo-1-azabicyclo[3.2.0]-heptane-2-carboxylate. The compound obtained was dissolved in acetonitrile (10 ml) and cooled to 0°~2° C. under atmosphere of nitrogen. To this solution were added diphenyl phosphorochloridate (0.56 ml) and N,N-diisopropyl-N-ethylamine (0.49 ml) successively and the mixture was stirred at 0° C. for 40 minutes. To the resulting solution were added dropwise a solution of (2S,4S)-4-mercapto-1-(4-nitrobenzyloxycarbonyl)-2-{4,5,6,7-tetrahydropyrazolo [1,5-a]pyrimidin-4-yl}-methylpyrrolidine (1.62 g) in acetonitrile (5 ml) and N,N-diisopropyl-N-ethylamine (0.77 ml) with stirring at 0°~2° C. and the mixture was stirred at the same temperature for 3 hours. To the reaction mixture was added ethyl acetate (80 ml) and the solution was washed with water and saturated aqueous sodium chloride successively, dried over anhydrous magnesium sulfate and evaporated in vacuo. The resulting residue was chromatographed on silica gel (150 g) eluting with a mixture of dichloromethane and acetone 1, V/V). The fractions containing the desired compound were collected and concentrated in vacuo to give 4-nitrobenzyl (4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-3-[(2S,4S) -1-(4-nitrobenzyloxycarbonyl)-2-{4,5,6,7-tetrahydropyrazolo [1,5-a]pyrimidin-4-yl}methyl pyrrolidin-4-yl]thio-7-oxo-1-azabicyclo[3,2,0]hept-2-ene-2-carboxylate (0.79 g).

Provenance & Evidence