Reaktion #65562

ord-6ce640c35c0849ea94ec5e2e846c85a2

Reaktionsgleichung

C[C@@H](O)[C@H]1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(S[C@H]3C[C@@H](c4csc(N)n4)N(C(=O)OCc4ccc([N+](=O)[O-])cc4)C3)[C@H](C)[C@H]12
4-nitrobenzyl (4R,5S,6S)-3-[(2S,4S)-2- (2-aminothiazol-4-yl)-1-(4-nitrobenzyloxycarbonyl)-pyrrolidin-4-ylthio]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo [3.2.0]hept-2-ene-2-carboxylate
O=P([O-])([O-])[O-]
phosphate
[H][H]
hydrogen
→
C[C@@H](O)[C@H]1C(=O)N2C(C(=O)O)=C(S[C@@H]3CN[C@H](c4csc(N)n4)C3)[C@H](C)[C@H]12
(4R,5S,6S)-3-[(2S,4S)-2-(2-aminothiazol-4-yl) -pyrrolidin-4-ylthio]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo [3.2.0]hept-2-ene-2-carboxylic acid
Ausbeute 45.7%

Edukte

C[C@@H](O)[C@H]1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(S[C@H]3C[C@@H](c4csc(N)n4)N(C(=O)OCc4ccc([N+](=O)[O-])cc4)C3)[C@H](C)[C@H]12
4-nitrobenzyl (4R,5S,6S)-3-[(2S,4S)-2- (2-aminothiazol-4-yl)-1-(4-nitrobenzyloxycarbonyl)-pyrrolidin-4-ylthio]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo [3.2.0]hept-2-ene-2-carboxylate
O=P([O-])([O-])[O-]
phosphate
[H][H]
hydrogen

Reagenzien

[OH-].[OH-].[Pd+2]
palladium hydroxide on carbon

Lösungsmittel

C1CCOC1
tetrahydrofuran

Reaktionsbedingungen

Detaillierte Bedingungen
See reaction.notes.procedure_details.

Aufarbeitung

  1. 1
    FiltrationAfter the catalyst was filtered off
  2. 2
    Einengenthe filtrate was concentrated
  3. 3
    Sonstigeto remove the organic solvent
  4. 4
    WaschenThe residue was washed with ethyl acetate
  5. 5
    Einengenconcentrated in vacuo
  6. 6
    Sonstigeto remove the organic solvent
  7. 7
    SonstigeThe residue was chromatographed on nonionic adsorption resin "Diaion
  8. 8
    Waschen" (Trademark, made by Mitsubishi Chemical Industries) (60 ml) eluting in turn with water (250 ml) and 5-7% aqueous acetone (200 ml)
  9. 9
    workup.ADDITIONThe fractions containing the desired compound
  10. 10
    Sonstigewere collected

Vorschrift

A mixture of 4-nitrobenzyl (4R,5S,6S)-3-[(2S,4S)-2- (2-aminothiazol-4-yl)-1-(4-nitrobenzyloxycarbonyl)-pyrrolidin-4-ylthio]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo [3.2.0]hept-2-ene-2-carboxylate (900 mg), 20% palladium hydroxide on carbon (350 mg), 0.05M phosphate buffer (pH 6.5, 20 ml) and tetrahydrofuran (30 ml) was stirred at room temperature for 3 hours under atmospheric pressure of hydrogen. After the catalyst was filtered off, the filtrate was concentrated to remove the organic solvent. The residue was washed with ethyl acetate, adjusted to pH 6.2 with aqueous potassium carbonate and concentrated in vacuo to remove the organic solvent. The residue was chromatographed on nonionic adsorption resin "Diaion HP-20" (Trademark, made by Mitsubishi Chemical Industries) (60 ml) eluting in turn with water (250 ml) and 5-7% aqueous acetone (200 ml). The fractions containing the desired compound were collected and lyophilized to give (4R,5S,6S)-3-[(2S,4S)-2-(2-aminothiazol-4-yl) -pyrrolidin-4-ylthio]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo [3.2.0]hept-2-ene-2-carboxylic acid (233 mg).

Quelle

DOI: 10.6084/m9.figshare.5104873.v1Patent: US05420122uspto-grants-1995_05