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

HRID 703597Notes

Reaction equation

HRID 703597 reaction equation
[N+](=[C:3]([C:17](=O)[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-].P(Cl)(OC1C=CC=CC=1)(OC1C=CC=CC=1)=O.C(N(C(C)C)CC)(C)C.[F:55][CH2:56][CH2:57][O:58][CH2:59][C@@H:60]1[CH2:64][C@H:63]([SH:65])[CH2:62][N:61]1[C:66]([O:68][CH2:69][C:70]1[CH:75]=[CH:74][C:73]([N+:76]([O-:78])=[O:77])=[CH:72][CH:71]=1)=[O:67]>ClC(Cl)C.C(#N)C.C([O-])(=O)C.[Rh+2].C([O-])(=O)C.C(OCC)(=O)C.O>[F:55][CH2:56][CH2:57][O:58][CH2:59][C@@H:60]1[CH2:64][C@H:63]([S:65][C:17]2[C@H:18]([CH3:19])[C@H:20]3[N:21]([C:22](=[O:27])[C@@H:23]3[C@H:24]([OH:26])[CH3:25])[C:3]=2[C:4]([O:6][CH2:7][C:8]2[CH:9]=[CH:10][C:11]([N+:14]([O-:16])=[O:15])=[CH:12][CH:13]=2)=[O:5])[CH2:62][N:61]1[C:66]([O:68][CH2:69][C:70]1[CH:71]=[CH:72][C:73]([N+:76]([O-:78])=[O:77])=[CH:74][CH:75]=1)=[O:67]

Participants

10

Reactant 4

HCID 75654Diphenyl chlorophosphateHCID 81531Diisopropylethylamine2×HCID 14884036(2S,4S)-2-(2-fluoroethyloxymethyl)-4-mercapto-1-(4-nitrobenzyloxycarbonyl)pyrrolidineHCID 57009450(R)-4-Nitrobenzyl 2-diazo-4-((2R,3S)-3-((R)-1-hydroxyethyl)-4-oxoazetidin-2-yl)-3-oxopentanoate

Product 1

HCID 571170454-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-carboxylateYield 48.7%

Reagents, catalysts & solvents 5

HCID 21674Acetic acid, rhodium(2+) saltCatalystHCID 962WaterSolventHCID 6342AcetonitrileSolvent2×HCID 63651,1-DichloroethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

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).

Workup

  1. temperatureunder refluxing in a nitrogen stream
  2. temperatureAfter refluxing for 1 hour
  3. concentrationthe mixture was concentrated under reduced pressure
  4. customto give a residue
  5. customsuccessively at -20° C
  6. stirringThe mixture was stirred at the same condition for 30 minutes
  7. waitat 0°-10° C. for 3 hours
  8. customThe organic layer was separated
  9. washwashed with brine
  10. dry with materialdried over magnesium sulfate
  11. concentrationconcentrated under reduced pressure
  12. customto give a syrup
  13. washeluted with a mixture of acetone and dichloromethane (5:95

Sources & evidence

ORD record
ord-ee6cc4ca30354240861419efd93418b6
Source dataset
uspto-grants-1991_01
Patent number
US04983596

Reaction notes

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