(R)-4-Nitrobenzyl 2-diazo-4-((2R,3S)-3-((R)-1-hydroxyethyl)-4-oxoazetidin-2-yl)-3-oxopentanoate → 4-nitrobenzyl (4R,5S,6S)-6-[(1R)-1-hydroxyethyl]4-methyl-3,7-dioxo-1-azabicyclo[3.2.0]heptane-2-carboxylate

HRID 37285

반응식

HRID 37285 반응식
[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([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]

참가 물질

4

반응물 1

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

생성물 1

HCID 572368784-nitrobenzyl (4R,5S,6S)-6-[(1R)-1-hydroxyethyl]4-methyl-3,7-dioxo-1-azabicyclo[3.2.0]heptane-2-carboxylate

시약·촉매·용매 2

HCID 21674Acetic acid, rhodium(2+) salt촉매HCID 111,2-Dichloroethane용매

실험 절차

To a solution of 4-nitrobenzyl (4R)-2-diazo-4-[(2R, 3S)-3-{(1R)-1-hydroxyethyl}-4-oxoazetidin-2-yl]-3-oxopentanoate (0.60 g) in 1,2-dichloroethane (15 ml) was added rhodium(II) acetate (2 mg) under reflux. The mixture was refluxed for 30 minutes under nitrogen atmosphere and concentrated under reduced pressure to give 4-nitrobenzyl (4R, 5S, 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 acetonitrile (15 ml) and N,N-diisopropyl-N-ethylamine (0.32 ml). Diphenyl phosphorochloridate (0.33 ml) was added thereto at -10°∫-5° C. in a nitrogen stream, followed by stirring at the same temperature for 30 minutes. To the solution were added N,N-diisopropyl-N-ethylamine (0.32 ml) and a solution of a mixture of (2S ,4S)-4-mercapto-2-(1-methyl-1H-tetrazol-5-yl) -1-(4-nitrobenzyloxycarbonyl)pyrrolidine and (2S, 4S)-4-mercapto-2-(2-methyl-2H-tetrazol-5-yl)-1-(4-nitrobenzyloxycarbonyl)pyrrolidine (0.55 g) in acetonitrile (2 ml) successively at -20° C. The mixture was stirred at the same temperature for 30 minutes and at 0°-10° C. for 3 hours. The mixture was poured into ethyl acetate (150 ml) and water (100 ml). The organic layer was separated, 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 (10: 90, V/V) to give 4-nitrobenzyl (4R,5S ,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-3-[(2S, 4S)-2{1(or 2)-methyl-1H(or 2H)-tetrazol-5-yl}-1-(4-nitrobenzyloxycarbonyl) pyrrolidin-4-yl]thio-7-oxo-1-azabicyclo [3.2.0]hept-2-ene-2-carboxylate (isomer A) (0.32 g).

후처리

  1. temperatureunder reflux
  2. temperatureThe mixture was refluxed for 30 minutes under nitrogen atmosphere
  3. concentrationconcentrated under reduced pressure

출처 및 근거

ORD 기록
ord-d9e3ee6c8d884b0e9c5544b47eb4c599
출처 데이터셋
uspto-grants-1995_05
특허 번호
US05420122

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