(3S,4R)-3-[(R)-1-hydroxyethyl]-4-[(R)-1-methyl-3-diazo-3-allyloxycarbonyl-2-oxopropyl]-2-azetidinone → allyl (4R,5R,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-3,7-dioxo-1-azabicyclo[3.2.0]heptane-2-carboxylate

To a solution of allyl (4R)-2-diazo-4-[(2R,3S)-3-{(1R)-1-hydroxyethyl}-4-oxoazetidin-2-yl]-3-oxopentanoate (0.5 g) in dichloromethane (10 ml) was added rhodium(II) octanoate (13.2 mg) under reflux. After refluxing for 20 minutes, to the solution was added rhodium(II) octanoate (13.2 mg). The mixture was refluxed for 40 minutes. The reaction mixture was cooled and evaporated in vacuo to give a residue. The residue was dissolved in anhydrous acetonitrile (10 ml) and then evaporated. This operation was repeated once again and the resulting residue was dried in vacuo to give allyl (4R,5R,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-3,7-dioxo-1-azabicyclo-[3.2.0]heptane-2-carboxylate. The residue containing the compound obtained above was dissolved in anhydrous acetonitrile (10 ml) and cooled to 0°-2° C. under an atmosphere of nitrogen. To this solution were added diphenyl phosphorochloridate (0.53 ml) and N,N-diisopropyl-N-ethylamine (0.47 ml) successively and the solution was stirred at 0°-2° C. for 40 minutes. To the resulting solution were added dropwise a solution of (2S,4S)-1-allyloxycarbonyl-4-mercapto-2-[(2-ureidoethyl)oxymethyl]pyrrolidine (0.62 g) in acetonitrile (10 ml) and N,N-diisopropyl-N-ethylamine (0.38 ml) successively with stirring at 2°-5° C., and the stirring was continued at the same temperature for 2 hours. To a reaction mixture was added ethyl acetate (30 ml) and water (10 ml) with stirring, and the organic layer was separated. This layer was washed with saturated aqueous sodium chloride solution (30 ml×2), dried over magnesium sulfate and evaporated in vacuo. The residue was chromatographed on silica gel (50 g) eluting with a mixture of chloroform and methanol (9:1 V/V). The fractions containing the desired compound were collected and evaporated in vacuo to give allyl (4R,5S,6S)-3-[(2S, 4S)-1-allyloxycarbonyl-2-{(2-ureidoethyl)oxymethyl}-pyrrolidin-4-yl]thio-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate (160 mg).

1. temperatureunder reflux
2. temperatureAfter refluxing for 20 minutes, to the solution
3. temperatureThe mixture was refluxed for 40 minutes
4. temperatureThe reaction mixture was cooled
5. customevaporated in vacuo
6. customto give a residue
7. customevaporated
8. customthe resulting residue was dried in vacuo

ORD record

ord-9241344a52854df484f7ddc9d657fbab

Source dataset

uspto-grants-1989_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04822787