Diphenylphosphinic chloride → 4-nitrobenzyl (1R, 5S, 6S)-2-[(2S, 4S)-2-[4-(N-4-nitrobenzyloxycarbonylacetimidoyl)piperazin-1-ylcarbonyl]-1-(4-nitrobenzyloxycarbonyl)pyrrolidin-4-ylthio]-6-[(1R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylate

HRID 361994

Reaktionsgleichung

Reaktionsgleichung von HRID 361994
C1(P(Cl)(C2C=CC=CC=2)=O)C=CC=CC=1.[OH:16][C@@H:17]([C@H:19]1[C:40](=[O:41])[N:21]2[CH:22]([C:27]([O:29][CH2:30][C:31]3[CH:36]=[CH:35][C:34]([N+:37]([O-:39])=[O:38])=[CH:33][CH:32]=3)=[O:28])[C:23](=O)[C@H:24]([CH3:25])[C@H:20]12)[CH3:18].FC(F)(F)S(O)(=O)=O.[SH:50][C@@H:51]1[CH2:55][N:54]([C:56]([O:58][CH2:59][C:60]2[CH:65]=[CH:64][C:63]([N+:66]([O-:68])=[O:67])=[CH:62][CH:61]=2)=[O:57])[C@H:53]([C:69]([N:71]2[CH2:76][CH2:75][N:74]([C:77](=[N:79][C:80]([O:82][CH2:83][C:84]3[CH:89]=[CH:88][C:87]([N+:90]([O-:92])=[O:91])=[CH:86][CH:85]=3)=[O:81])[CH3:78])[CH2:73][CH2:72]2)=[O:70])[CH2:52]1>C(#N)C.C(N(C(C)C)CC)(C)C>[N+:90]([C:87]1[CH:86]=[CH:85][C:84]([CH2:83][O:82][C:80]([N:79]=[C:77]([N:74]2[CH2:73][CH2:72][N:71]([C:69]([C@@H:53]3[CH2:52][C@H:51]([S:50][C:23]4[C@H:24]([CH3:25])[C@@H:20]5[C@@H:19]([C@H:17]([OH:16])[CH3:18])[C:40](=[O:41])[N:21]5[C:22]=4[C:27]([O:29][CH2:30][C:31]4[CH:32]=[CH:33][C:34]([N+:37]([O-:39])=[O:38])=[CH:35][CH:36]=4)=[O:28])[CH2:55][N:54]3[C:56]([O:58][CH2:59][C:60]3[CH:61]=[CH:62][C:63]([N+:66]([O-:68])=[O:67])=[CH:64][CH:65]=3)=[O:57])=[O:70])[CH2:76][CH2:75]2)[CH3:78])=[O:81])=[CH:89][CH:88]=1)([O-:92])=[O:91]

Komponenten

6

Edukt 3

HCID 73910Diphenylphosphinic chlorideHCID 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)-HCID 88299227(2S, 4S)-4-mercapto-2-[4-(N-4-nitrobenzyloxycarbonylacetimidoyl)piperazin-1-ylcarbonyl]-1-(4-nitrobenzyloxycarbonyl)pyrrolidine trifluoromethanesulfonate

Produkt 1

HCID 1317204064-nitrobenzyl (1R, 5S, 6S)-2-[(2S, 4S)-2-[4-(N-4-nitrobenzyloxycarbonylacetimidoyl)piperazin-1-ylcarbonyl]-1-(4-nitrobenzyloxycarbonyl)pyrrolidin-4-ylthio]-6-[(1R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylateAusbeute 21,6 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6342AcetonitrileLösungsmittel2×HCID 81531DiisopropylethylamineLösungsmittel2×

Versuchsvorschrift

127 μl of diphenylphosphoryl chloride and 108 μl of diisopropylethylamine were added dropwise, whilst ice-cooling, to a solution of 210 mg of 4-nitrobenzyl (1R, 5R, 6S)-6-[(1R)-1-hydroxyethyl]-1-methyl-2-oxo-1-carbapenam-3-carboxylate in 2.6 ml of dry acetonitrile, and the resulting mixture was stirred at the same temperature for 1 hour. At the end of this time, a solution of 450 mg of (2S, 4S)-4-mercapto-2-[4-(N-4-nitrobenzyloxycarbonylacetimidoyl)piperazin-1-ylcarbonyl]-1-(4-nitrobenzyloxycarbonyl)pyrrolidine trifluoromethanesulfonate (prepared as described in Preparation 1) in 2.4 ml of dry acetonitrile and 274 μl of diisopropylethylamine were simultaneously added dropwise to the mixture, whilst ice-cooling, and the mixture was allowed to stand overnight at the same temperature. The reaction mixture was then concentrated by evaporation under reduced pressure, and the concentrate was diluted with ethyl acetate. The diluted solution was washed, in turn, with water and with an aqueous solution of sodium chloride, after which it was dried over anhydrous magnesium sulfate. The solvent was then removed by distillation under reduced pressure, and the resulting residue was purified by column chromatography through 100 ml of silica gel 60 (Merck Art No. 9385), using a 10:5:2 by volume mixture of ethyl acetate, methylene chloride and methanol as the eluent. Those fractions containing the title compound were combined and concentrated by evaporation under reduced pressure, to give 120 mg of the title compound, as an amorphous solid.

Aufarbeitung

  1. temperaturecooling
  2. waitto stand overnight at the same temperature
  3. concentrationThe reaction mixture was then concentrated by evaporation under reduced pressure
  4. additionthe concentrate was diluted with ethyl acetate
  5. washThe diluted solution was washed, in turn, with water and with an aqueous solution of sodium chloride
  6. dry with materialafter which it was dried over anhydrous magnesium sulfate
  7. customThe solvent was then removed by distillation under reduced pressure
  8. customthe resulting residue was purified by column chromatography through 100 ml of silica gel 60 (Merck Art No. 9385)
  9. additionby volume mixture of ethyl acetate, methylene chloride and methanol as the eluent
  10. additionThose fractions containing the title compound
  11. concentrationconcentrated by evaporation under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-e1e56a7db50b4aad9d1e3e81fd51ec42
Quelldatensatz
uspto-grants-1999_02
Patentnummer
US05866564

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