Phosphate → HCID 10386735, compound

HRID 346378Notes

Reaction equation

HRID 346378 reaction equation
[F:1][CH:2]([F:49])[S:3][CH2:4][C@@H:5]1[CH2:9][C@H:8]([S:10][C:11]2[C@H:17]([CH3:18])[C@H:16]3[N:13]([C:14](=[O:22])[C@@H:15]3[C@H:19]([OH:21])[CH3:20])[C:12]=2[C:23]([O:25]CC2C=CC([N+]([O-])=O)=CC=2)=[O:24])[CH2:7][N:6]1C(OCC1C=CC([N+]([O-])=O)=CC=1)=O.P([O-])([O-])([O-])=O.[H][H]>[OH-].[OH-].[Pd+2].O1CCCC1>[F:49][CH:2]([F:1])[S:3][CH2:4][C@@H:5]1[CH2:9][C@H:8]([S:10][C:11]2[C@H:17]([CH3:18])[C@H:16]3[N:13]([C:14](=[O:22])[C@@H:15]3[C@H:19]([OH:21])[CH3:20])[C:12]=2[C:23]([OH:25])=[O:24])[CH2:7][NH:6]1

Participants

6

Reactant 3

HCID 1061PhosphateHCID 10604931HCID 10604931, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 10386735HCID 10386735, compoundYield 58%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 4-nitrobenzyl (4R,5S,6S)-3-[(2S,4S)-2-(difluoromethyl)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 (0.58 g), 20% palladium hydroxide on carbon (0.5 g), 0.05M phosphate buffer (pH 6.3, 18 ml) and tetrahydrofuran (18 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 aqueous residue was washed with ethyl acetate (10 ml×2) 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 (80 ml) and 6% aqueous acetone (80 ml). The fractions containing the desired compound were collected and lyophilized to give (4R,5S,6S)-3-[(2S,4S)-2-(difluoromethyl)thiomethylpyrrolidin-4-ylthio]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid (0.19 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 aqueous residue was washed with ethyl acetate (10 ml×2)
  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 (80 ml) and 6% aqueous acetone (80 ml)
  9. additionThe fractions containing the desired compound
  10. customwere collected

Sources & evidence

ORD record
ord-9f17137806a145c6879052fadf768378
Source dataset
uspto-grants-1991_10
Patent number
US05061804

Reaction notes

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