Phosphate → HCID 10669544, compound

HRID 1088993Notes

Reaction equation

HRID 1088993 reaction equation
[C:1]([CH2:4][S:5][CH2:6][C@@H:7]1[CH2:11][C@H:10]([S:12][C:13]2[C@H:19]([CH3:20])[C@H:18]3[N:15]([C:16](=[O:24])[C@@H:17]3[C@H:21]([OH:23])[CH3:22])[C:14]=2[C:25]([O:27]CC2C=CC([N+]([O-])=O)=CC=2)=[O:26])[CH2:9][N:8]1C(OCC1C=CC([N+]([O-])=O)=CC=1)=O)(=[O:3])[NH2:2].P([O-])([O-])([O-])=O.[H][H]>[OH-].[OH-].[Pd+2].O1CCCC1>[C:1]([CH2:4][S:5][CH2:6][C@@H:7]1[CH2:11][C@H:10]([S:12][C:13]2[C@H:19]([CH3:20])[C@H:18]3[N:15]([C:16](=[O:24])[C@@H:17]3[C@H:21]([OH:23])[CH3:22])[C:14]=2[C:25]([OH:27])=[O:26])[CH2:9][NH:8]1)(=[O:3])[NH2:2]

Participants

6

Reactant 3

HCID 1061PhosphateHCID 11803031HCID 11803031, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 10669544HCID 10669544, compoundYield 66.9%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 4-nitrobenzyl (4R,5S,6S)-3-[(2S,4S)-2-(carbamoylmethyl)thiomethyl-1-(4-nitrobenzyloxycarbonyl)pyrrolidin-4-ylthio]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate (0.42 g), 20% palladium hydroxide on carbon (0.4 g), 0.05M phosphate buffer (pH 6.3, 20 ml), and tetrahydrofuran (20 ml) was stirred at ambient temperature for 4 hours under atmospheric pressure of hydrogen. After the catalyst was filtered off, the filtrate was concentrated under reduced pressure to remove the organic solvent. The resulting residue was washed twice with ethyl acetate (20 ml) and the aqueous layer was concentrated under reduced pressure 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 (100 ml) and 5% aqueous acetone (100 ml). The fractions containing the desired compound were collected and lyophilized to give (4R,5S,6S)-3-[(2S,4S)-2-(carbamoylmethyl)thiomethylpyrrolidin-4-ylthio]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid (0.16 g).

Workup

  1. filtrationAfter the catalyst was filtered off
  2. concentrationthe filtrate was concentrated under reduced pressure
  3. customto remove the organic solvent
  4. washThe resulting residue was washed twice with ethyl acetate (20 ml)
  5. concentrationthe aqueous layer was concentrated under reduced pressure
  6. customto remove the organic solvent
  7. customThe residue was chromatographed on nonionic adsorption resin "Diaion
  8. wash" (Trademark, made by Mitsubishi Chemical Industries) (20 ml) eluting in turn with water (100 ml) and 5% aqueous acetone (100 ml)
  9. additionThe fractions containing the desired compound
  10. customwere collected

Sources & evidence

ORD record
ord-4359043b116540c08f52f3ca0ea256fb
Source dataset
uspto-grants-1990_10
Patent number
US04963543

Reaction notes

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