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Phosphoric Acid → (4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-3-[(2S,4S)-2-(4-methyl-2-oxoimidazolidin-1-yl)methylpyrrolidin-4-yl]thio-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid

HRID 1650868
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1650868
[OH:1][C@@H:2]([C@H:4]1[C:10](=[O:11])[N:9]2[C@@H:5]1[C@@H:6]([CH3:45])[C:7]([S:18][C@@H:19]1[CH2:23][N:22](C(OCC3C=CC([N+]([O-])=O)=CC=3)=O)[C@H:21]([CH2:37][N:38]3[CH2:42][CH:41]([CH3:43])[NH:40][C:39]3=[O:44])[CH2:20]1)=[C:8]2[C:12]([O:14]CC=C)=[O:13])[CH3:3].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(OCC)(=O)CCCCC.[Na].P(=O)(O)(O)O.[H][H]>O1CCCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[OH-].[OH-].[Pd+2]>[OH:1][C@@H:2]([C@H:4]1[C:10](=[O:11])[N:9]2[C@@H:5]1[C@@H:6]([CH3:45])[C:7]([S:18][C@@H:19]1[CH2:23][NH:22][C@H:21]([CH2:37][N:38]3[CH2:42][CH:41]([CH3:43])[NH:40][C:39]3=[O:44])[CH2:20]1)=[C:8]2[C:12]([OH:14])=[O:13])[CH3:3]
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Komponenten

9

Edukt 5

HCID 1004Phosphoric AcidHCID 11776TriphenylphosphineHCID 53628222Sodium 2-ethyl hexanoateHCID 86743935allyl (4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-3-{(2S,4S)-2-(4-methyl-2-oxoimidazolidin-1-yl)methyl-1-(4-nitrobenzyloxycarbonyl)pyrrolidin-4-yl]thio-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylateHCID 178418361HCID 178418361, Verbindung

Produkt

1
HCID 15056096(4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-3-[(2S,4S)-2-(4-methyl-2-oxoimidazolidin-1-yl)methylpyrrolidin-4-yl]thio-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acidAusbeute 17,9 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 9942167Palladium hydroxideKatalysatorHCID 178418397HCID 178418397, VerbindungKatalysatorHCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

To a solution of allyl (4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-3-{(2S,4S)-2-(4-methyl-2-oxoimidazolidin-1-yl)methyl-1-(4-nitrobenzyloxycarbonyl)pyrrolidin-4-yl]thio-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate (2.45 g) in tetrahydrofuran (50 ml) were added triphenylphosphine (0.50 g), sodium 2-ethyl hexanoate (0.70 g) and tetrakis(triphenylphosphine)palladium(0) (0.22 g) successively with stirring at ambient temperature. After stirring at the same temperature for 1 hour, the reaction mixture was evaporated in vacuo to give a residue. A mixture of the residue, 20% palladium hydroxide on carbon (0.5 g), 0.1M phosphoric acid buffer (pH=6.0, 80 ml) and tetrahydrofuran (80 ml) was stirred for 5 hours under atmospheric pressure of hydrogen at ambient temperature. After the catalyst was filtered off, the filtrate was 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) (30 ml) eluting in turn with water (90 ml) and 5% aqueous acetone (100 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-(4-methyl-2-oxoimidazolidin-1-yl)methylpyrrolidin-4-yl]thio-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid (0.29 g).

Aufarbeitung

  1. stirringAfter stirring at the same temperature for 1 hour
  2. customthe reaction mixture was evaporated in vacuo
  3. customto give a residue
  4. filtrationAfter the catalyst was filtered off
  5. customthe filtrate was evaporated 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) (30 ml) eluting in turn with water (90 ml) and 5% aqueous acetone (100 ml)
  9. additionThe fractions containing the desired compound
  10. customwere collected

Quellen und Nachweise

ORD-Eintrag
ord-64e077e4d7084016b5685ffc1afd5b4d
Quelldatensatz
uspto-grants-1990_05
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US04925838

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