Diisopropylethylamine → p-nitrobenzyl (1R,5S,6S)-2-(1-{4-[(furan-2-carbonylamino)methyl]-1,3-thiazol-2-yl}azetidin-3-yl)thio-6-[(R)-1-hydroxyethyl)-1-methylcarbapen-2-em-3-carboxylate

HRID 891533Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 891533
C([S:4][CH:5]1[CH2:8][N:7]([C:9]2[S:10][CH:11]=[C:12]([CH2:14][NH:15][C:16]([C:18]3[O:19][CH:20]=[CH:21][CH:22]=3)=[O:17])[N:13]=2)[CH2:6]1)(=O)C.C(O)(=O)C.NN.C1(P(O[C:44]2[C@H:45]([CH3:68])[C@H:46]3[C@@H:63]([C@H:64]([OH:66])[CH3:65])[C:62](=[O:67])[N:47]3[C:48]=2[C:49]([O:51][CH2:52][C:53]2[CH:58]=[CH:57][C:56]([N+:59]([O-:61])=[O:60])=[CH:55][CH:54]=2)=[O:50])(C2C=CC=CC=2)=O)C=CC=CC=1.C(N(C(C)C)CC)(C)C.C(=O)([O-])O.[Na+]>CN(C)C=O.C(#N)C.C(OCC)(=O)C>[O:19]1[CH:20]=[CH:21][CH:22]=[C:18]1[C:16]([NH:15][CH2:14][C:12]1[N:13]=[C:9]([N:7]2[CH2:6][CH:5]([S:4][C:44]3[C@H:45]([CH3:68])[C@@H:46]4[C@@H:63]([C@H:64]([OH:66])[CH3:65])[C:62](=[O:67])[N:47]4[C:48]=3[C:49]([O:51][CH2:52][C:53]3[CH:54]=[CH:55][C:56]([N+:59]([O-:61])=[O:60])=[CH:57][CH:58]=3)=[O:50])[CH2:8]2)[S:10][CH:11]=1)=[O:17]

Komponenten

9

Edukt 5

HCID 81531DiisopropylethylamineHCID 165591Hydrazine, acetate (1:1)HCID 516892Sodium BicarbonateHCID 222429283-Acetylthio-1-[4-(furan-2-carbonylamino)methyl-1,3-thiazol-2-yl]azetidineHCID 131720384p-nitrobenzyl (1R,5S,6S)-2-(diphenylphosphoryloxy)-6-[(R)-1-hydroxyethyl)-1-methylcarbapen-2-em-3-carboxylate

Produkt 1

HCID 131725349p-nitrobenzyl (1R,5S,6S)-2-(1-{4-[(furan-2-carbonylamino)methyl]-1,3-thiazol-2-yl}azetidin-3-yl)thio-6-[(R)-1-hydroxyethyl)-1-methylcarbapen-2-em-3-carboxylateAusbeute 89,5 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6228DimethylformamideLösungsmittelHCID 6342AcetonitrileLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

To a solution of 3-acetylthio-1-{4-[(furan-2-carbonylamino)methyl]-1,3-thiazol-2-yl}azetidine (341 mg, 1.12 mmol) (obtained as described in Reference Example 67) in dimethylformamide (10 ml) was added hydrazine acetate (123 mg, 1.34 mmol) at room temperature under an atmosphere of nitrogen and the mixture was stirred for 1 hour. After checking the completion of the reaction, a solution of p-nitrobenzyl (1R,5S,6S)-2-(diphenylphosphoryloxy)-6-[(R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylate (797 mg, 1.34 mmol) in acetonitrile (20 ml) was added dropwise into the resulting mixture in an ice bath under an atmosphere of nitrogen, followed by the addition of diisopropylethylamine (0.78 ml, 4.48 mmol). The mixture was stirred for 3 hours while gradually raising the temperature to room temperature. After checking the completion of the reaction, ethyl acetate and saturated aqueous sodium hydrogencarbonate solution were added to the reaction mixture. The resulting mixture was shaken in a separatory funnel and the ethyl acetate layer was separated, washed with 0.5 M hydrochloric acid, saturated aqueous sodium hydrogencarbonate solution and saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by chromatography on a silica gel column (eluant: ethyl acetate) to afford p-nitrobenzyl (1R,5S,6S)-2-(1-{4-[(furan-2-carbonylamino)methyl]-1,3-thiazol-2-yl}azetidin-3-yl)thio-6-[(R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylate (641 mg, yield 89%) as a pale yellow solid.

Aufarbeitung

  1. customthe completion of the reaction
  2. stirringThe mixture was stirred for 3 hours
  3. additionwere added to the reaction mixture
  4. stirringThe resulting mixture was shaken in a separatory funnel
  5. customthe ethyl acetate layer was separated
  6. washwashed with 0.5 M hydrochloric acid, saturated aqueous sodium hydrogencarbonate solution and saturated aqueous sodium chloride solution
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by chromatography on a silica gel column (eluant: ethyl acetate)

Quellen und Nachweise

ORD-Eintrag
ord-9408deeeb4d149b292014b78ca2b7410
Quelldatensatz
uspto-grants-2006_02
Patentnummer
US07001897B2

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