(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)-

HRID 1650864Notes

Reaction equation

HRID 1650864 reaction equation
[N+](=[C:3]([C:17](=[O:28])[C@@H:18]([C@@H:20]1[C@@H:23]([C@H:24]([OH:26])[CH3:25])[C:22](=[O:27])[NH:21]1)[CH3:19])[C:4]([O:6][CH2:7][C:8]1[CH:13]=[CH:12][C:11]([N+:14]([O-:16])=[O:15])=[CH:10][CH:9]=1)=[O:5])=[N-]>ClCCCl.C(#N)C.C([O-])(=O)C.[Rh+2].C([O-])(=O)C>[OH:26][C@@H:24]([C@H:23]1[C:22](=[O:27])[N:21]2[C@@H:20]1[C@@H:18]([CH3:19])[C:17](=[O:28])[CH:3]2[C:4]([O:6][CH2:7][C:8]1[CH:13]=[CH:12][C:11]([N+:14]([O-:16])=[O:15])=[CH:10][CH:9]=1)=[O:5])[CH3:25]

Participants

5

Reactant 1

HCID 57009450(R)-4-Nitrobenzyl 2-diazo-4-((2R,3S)-3-((R)-1-hydroxyethyl)-4-oxoazetidin-2-yl)-3-oxopentanoate

Product 1

HCID 98853021-Azabicyclo[3.2.0]heptane-2-carboxylic acid, 6-[(1R)-1-hydroxyethyl]-4-methyl-3,7-dioxo-, (4-nitrophenyl)methyl ester, (4R,5R,6S)-

Reagents, catalysts & solvents 3

HCID 21674Acetic acid, rhodium(2+) saltCatalystHCID 111,2-DichloroethaneSolventHCID 6342AcetonitrileSolvent

Procedure

To a solution of 4-nitrobenzyl (4R)-2-diazo-4-[(2R,3S)-3-{(1R)-1-hydroxyethyl}-4-oxoazetidin-2-yl]-3-oxopentanoate (1.50 g) in 1,2-dichloroethane (30 ml) was added rhodium(II) acetate (5 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 anhydrous acetonitrile (10 ml) and then 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 anhydrous acetonitrile (30 ml) and cooled to 0° C. under an atmosphere of nitrogen. To this solution were added diphenyl phosphorochloridate (0.84 ml) and N,N-diisopropyl-N-ethylamine (0.74 ml) successively and the solution was stirred at 0° C. for 40 minutes. To the resulting solution were added dropwise a solution of (2S,4S)-4-mercapto-2-(4-methylpiperazin-1-yl)methyl-1-(4-nitrobenzyloxycarbonyl)pyrrolidine (1.97 g) in acetonitrile (10 ml) and N,N-diisopropyl-N-ethylamine (0.87 ml) with stirring at 5° C., and the stirring was continued at the same temperature for 2 hours. To the reaction mixture was added ethyl acetate (50 ml) and water (20 ml) with stirring, and the organic layer was separated. This layer was washed with saturated aqueous sodium chloride solution (40 ml×3), dried over magnesium sulfate and evaporated. The residue was chromatographed on silica gel (100 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 4-nitrobenzyl (4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-3-[(2S,4S)-2-(4-methylpiperazin-1-yl)methyl-1-(4-nitrobenzyloxycarbonyl)pyrrolidin-4-yl]thio-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate (2.38 g).

Workup

  1. temperatureunder refluxing
  2. temperatureAfter refluxing for 30 minutes
  3. temperaturethe reaction mixture was cooled
  4. customevaporated in vacuo
  5. customto give a residue
  6. customevaporated
  7. customthe residue was dried in vacuo

Sources & evidence

ORD record
ord-71933103112f4cbab9b866d89bf15d07
Source dataset
uspto-grants-1990_05
Patent number
US04925838

Reaction notes

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