(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 1088991Notes

Reaction equation

HRID 1088991 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.C1C=CC=CC=1.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 241BenzeneSolvent

Procedure

To a solution of 4-nitrobenzyl (4R)-2-diazo-4-[(2R,3S)-3-{(1R)-1-hydroxyethyl}-4-oxoazetidin-2-yl]-3-oxopentanoate (0.4 g) in 1,2-dichloroethane was added rhodium(II) acetate (1 mg) under refluxing. After refluxing for 1 hour, the reaction mixture was cooled and evaporated in vacuo to give a residue. The residue was dissolved in anhydrous benzene (10 ml) and then evaporated in vacuo. 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 above was dissolved in anhydrous acetonitrile (10 ml) and cooled to 0° C. under an atmosphere of nitrogen. To this solution were added N,N-diisopropyl-N-ethylamine (0.21 ml) and diphenyl phosphorochloridate (0.22 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)-2-(carbamoylmethyl)thiomethyl-4-mercapto-1-(4-nitrobenzyloxycarbonyl)pyrrolidine (0.45 g) in N,N-dimethylformamide (3 ml) and N,N-diisopropyl-N-ethylamine (0.21 ml) at 0°-2° C. with stirring and the stirring was continued at the same temperature for 2 hours. To the reaction mixture was added ethyl acetate (30 ml). The solution was washed 3 times with saturated aqueous sodium chloride (20 ml), dried over anhydrous magnesium sulfate and evaporated in vacuo to give a residue. The residue was chromatographed on silica gel (60 g) eluting with a mixture of dichloromethane and acetone (1:1, V/V). The fractions containing the desired compound were collected and evaporated in vacuo to give 4-nitrobenzyl (4R,5S,6S)-3-[(2S,4S)-2-(carbamoylmethyl)thiomethyl-1-(4-nitrobenzyloxycarbonyl)pyrrolidin-4-ylthio]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate (0.44 g).

Workup

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

Sources & evidence

ORD record
ord-bfb7be6a27654d639b733d61a1839a2d
Source dataset
uspto-grants-1990_10
Patent number
US04963543

Reaction notes

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