Phosphate → HCID 18641575, compound

HRID 346382Notes

Reaction equation

HRID 346382 reaction equation
[CH3:1][N:2]1[C:6]([S:7][CH2:8][C@@H:9]2[CH2:13][C@H:12]([S:14][C:15]3[C@H:21]([CH3:22])[C@H:20]4[N:17]([C:18](=[O:26])[C@@H:19]4[C@H:23]([OH:25])[CH3:24])[C:16]=3[C:27]([O:29]CC3C=CC([N+]([O-])=O)=CC=3)=[O:28])[CH2:11][N:10]2C(OCC2C=CC([N+]([O-])=O)=CC=2)=O)=[N:5][N:4]=[N:3]1.P([O-])([O-])([O-])=O.[H][H]>[OH-].[OH-].[Pd+2].O1CCCC1>[OH:25][C@@H:23]([C@H:19]1[C:18](=[O:26])[N:17]2[C@@H:20]1[C@@H:21]([CH3:22])[C:15]([S:14][C@@H:12]1[CH2:11][NH:10][C@H:9]([CH2:8][S:7][C:6]3[N:2]([CH3:1])[N:3]=[N:4][N:5]=3)[CH2:13]1)=[C:16]2[C:27]([OH:29])=[O:28])[CH3:24]

Participants

6

Reactant 3

HCID 1061PhosphateHCID 57083059HCID 57083059, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 18641575HCID 18641575, compoundYield 49.3%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 4-nitrobenzyl (4R,5S,6S)-3-[(2S,4S)-2-(1-methyl-1H-tetrazol-5-yl)thiomethyl-1-(4-nitrobenzyloxycarbonyl)pyrrolidin-4-yl]thio-4-methyl-6-[(1R)- 1-hydroxyethyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate (0.80 g), 20% palladium hydroxide on carbon (0.5 g), 0.05M phosphate buffer (pH 6.3, 30 ml) and tetrahydrofuran (30 ml) was stirred for 3 hours under atmospheric pressure of hydrogen at ambient temperature. After the catalyst was filtered off, the filt-rate was concentrated under reduced pressure to remove the organic solvent. The residue was washed with ethyl acetate (30 ml×2) and evaporated in vacuo to remove the organic solvent. The residue was chromatographed on nonionic adsorption resin "Diaion HP-20" (Trademark, made by Mitsubishi Chemical Industries) (20 ml) eluting in turn with water (60 ml) and 10% aqueous acetone solution (120 ml). The fractions containing the desired compound were collected and lyophilized to give (4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-3-[(2S,4S)-2-{(1-methyl-1H-tetrazol-5-yl)thiomethyl}pyrrolidin-4-ylthio]-7-oxo-1 -azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid (0.23 g).

Workup

  1. filtrationAfter the catalyst was filtered off
  2. concentrationthe filt-rate was concentrated under reduced pressure
  3. customto remove the organic solvent
  4. washThe residue was washed with ethyl acetate (30 ml×2)
  5. customevaporated in vacuo
  6. customto remove the organic solvent
  7. customThe residue was chromatographed on nonionic adsorption resin "Diaion HP-20" (Trademark, made by Mitsubishi Chemical Industries) (20 ml)
  8. washeluting in turn with water (60 ml) and 10% aqueous acetone solution (120 ml)
  9. additionThe fractions containing the desired compound
  10. customwere collected

Sources & evidence

ORD record
ord-bfa023cf1c224db9bb37f8d7adb45d1e
Source dataset
uspto-grants-1991_10
Patent number
US05061804

Reaction notes

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