Hydrochloric Acid → benzhydryl (6R,7R)-7-[[(2Z)-2-[2-[(2-methylpropan-2-yl)oxycarbonylamino]-1,3-thiazol-4-yl]-2-trityloxyiminoacetyl]amino]-8-oxo-3-(pyridin-2-ylsulfanylmethylsulfanyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

HRID 1707447Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1707447
C([S:4][CH2:5][S:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][N:8]=1)(=O)C.C[O-].[Na+].CO.[C:18]1([CH:24]([O:31][C:32]([C:34]2[N:39]3[C:40](=[O:80])[C@@H:41]([NH:42][C:43](=[O:79])/[C:44](/[C:66]4[N:67]=[C:68]([NH:71][C:72]([O:74][C:75]([CH3:78])([CH3:77])[CH3:76])=[O:73])[S:69][CH:70]=4)=[N:45]\[O:46][C:47](C4C=CC=CC=4)([C:54]4[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=4)[C:48]4[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=4)[C@H:38]3[S:37][CH2:36][C:35]=2OS(C)(=O)=O)=[O:33])C2C=CC=CC=2)[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.Cl>CN(C)C=O.O1CCCC1.O>[C:18]1([CH:24]([O:31][C:32]([C:34]2[N:39]3[C:40](=[O:80])[C@@H:41]([NH:42][C:43](=[O:79])/[C:44](/[C:66]4[N:67]=[C:68]([NH:71][C:72]([O:74][C:75]([CH3:77])([CH3:76])[CH3:78])=[O:73])[S:69][CH:70]=4)=[N:45]\[O:46][C:47]([C:48]4[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=4)([C:48]4[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=4)[C:54]4[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=4)[C@H:38]3[S:37][CH2:36][C:35]=2[S:4][CH2:5][S:6][C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][N:8]=2)=[O:33])[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Komponenten

8

Edukt 4

HCID 313Hydrochloric AcidHCID 10260338benzhydryl (6R,7R)-7-[[(2Z)-2-[2-[(2-methylpropan-2-yl)oxycarbonylamino]-1,3-thiazol-4-yl]-2-trityloxyiminoacetyl]amino]-3-methylsulfonyloxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylateHCID 104653712-AcetylthiomethylthiopyridineHCID 23694274Sodium methanolate methanol

Produkt 1

HCID 16143732benzhydryl (6R,7R)-7-[[(2Z)-2-[2-[(2-methylpropan-2-yl)oxycarbonylamino]-1,3-thiazol-4-yl]-2-trityloxyiminoacetyl]amino]-8-oxo-3-(pyridin-2-ylsulfanylmethylsulfanyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylateAusbeute 145,8 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel2×HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

To a solution of 2-acetylthiomethylthiopyridine (249 mg: 1.25 mMol.) in a mixture of dimethylformamide (4 ml) and tetrahydrofuran (2 ml) cooling at -78° C. is added dropwise 1.26N-sodium methoxide-methanol solution (0.87 ml: 1.10 mMol.), and the mixture is stirred at -78° C. for 15 minutes. To this reaction mixture is added a solution of 7β-[(Z)-2-(2-t-butoxycarbonylaminothiazol-4-yl)-2-trityloxyiminoacetamido]-3-methanesulfonyloxy-3-cephem-4-carboxylic acid diphenylmethyl ester (971 mg: 1.00 mMol.) in dimethylformamide (2 ml) and the mixture is stirred at -78° C. for 1 hour. The reaction mixture is mixed with 10% hydrochloric acid to stop the reaction, diluted with water, and extracted with ethyl acetate. The extract is washed with dilute aqueous sodium hydrogen carbonate and brine, dried over sodium sulfate, and concentrated. The residue is purified by silica gel chromatography (toluene: ethyl acetate=4:1) and silica gel rechromatography (toluene: ethyl acetate=7:1) to give 7β-[(Z)-2-(2-t-butoxycarbonylaminothiazol-4-yl)-2-trityloxyiminoacetamido]-3-(pyrid-2-ylthiomethylthio)-3-cephem-4-carboxylic acid diphenylmethyl ester as colorless foam (753 mg). Yield: 73%.

Aufarbeitung

  1. stirringthe mixture is stirred at -78° C. for 1 hour
  2. customthe reaction
  3. extractionextracted with ethyl acetate
  4. washThe extract is washed with dilute aqueous sodium hydrogen carbonate and brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated
  7. customThe residue is purified by silica gel chromatography (toluene: ethyl acetate=4:1) and silica gel rechromatography (toluene: ethyl acetate=7:1)

Quellen und Nachweise

ORD-Eintrag
ord-28e6e66af4784d16969c27dd8bbd08da
Quelldatensatz
uspto-grants-1994_10
Patentnummer
US05352792

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