Phosphate → (5 R,6S)-3-[(2S,4S)-2-(2-aminothiazol-4-yl) pyrrolidin-4-ylthio]-6-[(1R)-1-hydroxyethyl]-7-oxo-1-azabicyclo [3.2.0]hept-2-ene-2-carboxylic acid

HRID 37283Notes

Reaction equation

HRID 37283 reaction equation
[NH2:1][C:2]1[S:3][CH:4]=[C:5]([C@@H:7]2[CH2:11][C@H:10]([S:12][C:13]3[CH2:19][C@H:18]4[N:15]([C:16](=[O:36])[C@@H:17]4[C@H:20]([O:22]C(OCC4C=CC([N+]([O-])=O)=CC=4)=O)[CH3:21])[C:14]=3[C:37]([O:39]CC3C=CC([N+]([O-])=O)=CC=3)=[O:38])[CH2:9][N:8]2C(OCC2C=CC([N+]([O-])=O)=CC=2)=O)[N:6]=1.P([O-])([O-])([O-])=O.[H][H]>[OH-].[OH-].[Pd+2].O1CCCC1>[NH2:1][C:2]1[S:3][CH:4]=[C:5]([C@@H:7]2[CH2:11][C@H:10]([S:12][C:13]3[CH2:19][C@H:18]4[N:15]([C:16](=[O:36])[C@@H:17]4[C@H:20]([OH:22])[CH3:21])[C:14]=3[C:37]([OH:39])=[O:38])[CH2:9][NH:8]2)[N:6]=1

Participants

6

Reactant 3

HCID 1061PhosphateHCID 14305051HCID 14305051, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 57212238(5 R,6S)-3-[(2S,4S)-2-(2-aminothiazol-4-yl) pyrrolidin-4-ylthio]-6-[(1R)-1-hydroxyethyl]-7-oxo-1-azabicyclo [3.2.0]hept-2-ene-2-carboxylic acidYield 65.5%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 4-nitrobenzyl (5R,6S)-3-[(2S,4S)-2-(2-aminothiazol-4-yl)-1-(4-nitrobenzyloxycarbonyl) pyrrolidin-4-ylthio]-6-[(1R)-1-(4-nitrobenzyloxycarbonyloxy) ethyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate (1.85 g), 20% palladium hydroxide on carbon (500 mg), 0.05M phosphate buffer (pH 6.5, 30 ml) and tetrahydrofuran (50 ml) was stirred at room temperature for 4 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 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 (300 ml) and 5% aqueous acetone (200 ml). The fractions containing the desired compound were collected and lyophilized to give (5 R,6S)-3-[(2S,4S)-2-(2-aminothiazol-4-yl) pyrrolidin-4-ylthio]-6-[(1R)-1-hydroxyethyl]-7-oxo-1-azabicyclo [3.2.0]hept-2-ene-2-carboxylic acid (540 mg).

Workup

  1. filtrationAfter the catalyst was filtered off
  2. concentrationthe filtrate was concentrated
  3. customto remove the organic solvent
  4. washThe residue was washed with ethyl acetate
  5. concentrationconcentrated
  6. customto remove the organic solvent
  7. customThe residue was chromatographed on nonionic adsorption resin "Diaion
  8. wash" (Trademark, made by Mitsubishi Chemical Industries) (60 ml) eluting in turn with water (300 ml) and 5% aqueous acetone (200 ml)
  9. additionThe fractions containing the desired compound
  10. customwere collected

Sources & evidence

ORD record
ord-61295b38502d4d3aa484aabc2be36a00
Source dataset
uspto-grants-1995_05
Patent number
US05420122

Reaction notes

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