Phosphate → (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

HRID 37284Notes

Reaction equation

HRID 37284 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[C@H:19]([CH3:20])[C@H:18]4[N:15]([C:16](=[O:24])[C@@H:17]4[C@H:21]([OH:23])[CH3:22])[C:14]=3[C:25]([O:27]CC3C=CC([N+]([O-])=O)=CC=3)=[O:26])[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[C@H:19]([CH3:20])[C@H:18]4[N:15]([C:16](=[O:24])[C@@H:17]4[C@H:21]([OH:23])[CH3:22])[C:14]=3[C:25]([OH:27])=[O:26])[CH2:9][NH:8]2)[N:6]=1

Participants

6

Reactant 3

HCID 1061PhosphateHCID 57238971HCID 57238971, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 57177244(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 acidYield 45.7%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

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).

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 in vacuo
  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 (250 ml) and 5-7% aqueous acetone (200 ml)
  9. additionThe fractions containing the desired compound
  10. customwere collected

Sources & evidence

ORD record
ord-6ce640c35c0849ea94ec5e2e846c85a2
Source dataset
uspto-grants-1995_05
Patent number
US05420122

Reaction notes

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