Phosphorus oxychloride → p-Nitrobenzyl 7-{2(2-formamido-4-thiazolyl)-2-methoxyiminoacetamido}-3-chloro-3-cephem-4-carboxylate

HRID 364524Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 364524
C[N+](C)=CCl.[Cl-].P(Cl)(Cl)(Cl)=O.[CH:12]([NH:14][C:15]1[S:16][CH:17]=[C:18]([C:20](=[N:24][O:25][CH3:26])[C:21]([OH:23])=O)[N:19]=1)=[O:13].[NH2:27][CH:28]1[C:49](=[O:50])[N:30]2[C:31]([C:36]([O:38][CH2:39][C:40]3[CH:45]=[CH:44][C:43]([N+:46]([O-:48])=[O:47])=[CH:42][CH:41]=3)=[O:37])=[C:32]([Cl:35])[CH2:33][S:34][C@H:29]12.C[Si](CC(N)=O)(C)C>C(OCC)(=O)C.O.CN(C)C=O>[CH:12]([NH:14][C:15]1[S:16][CH:17]=[C:18]([C:20](=[N:24][O:25][CH3:26])[C:21]([NH:27][CH:28]2[C:49](=[O:50])[N:30]3[C:31]([C:36]([O:38][CH2:39][C:40]4[CH:41]=[CH:42][C:43]([N+:46]([O-:48])=[O:47])=[CH:44][CH:45]=4)=[O:37])=[C:32]([Cl:35])[CH2:33][S:34][C@H:29]23)=[O:23])[N:19]=1)=[O:13]

Komponenten

9

Edukt 5

HCID 24813Phosphorus oxychlorideHCID 77311Chloro-N,N-dimethylformiminium chlorideHCID 357676Acetamide, 2-(trimethylsilyl)-HCID 27245112-(2-Formylamino-1,3-Thiazol-4-Yl)-2-(Methoxyimino)Acetic AcidHCID 676435564-Nitrobenzyl 7-amino-3-chloro-3-cephem-4-carboxylate

Produkt 1

HCID 131712431p-Nitrobenzyl 7-{2(2-formamido-4-thiazolyl)-2-methoxyiminoacetamido}-3-chloro-3-cephem-4-carboxylateAusbeute 80,8 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel2×

Versuchsvorschrift

Vilsmeier reagent prepared from dimethylformamide (0.22 g.) and phosphorus oxychloride (0.46 g.) was suspended in dry ethyl acetate (20 ml.). 2-(2-Formamido-4-thiazolyl)-2-methoxyiminoacetic acid (anti isomer, 0.62 g.) was added to the suspension under ice-cooling with stirring, and the mixture was stirred at the same temperature for 30 minutes to prepare the activated acid solution. The solution was added all at once to a solution of p-nitrobenzyl 7-amino-3-chloro-3-cephem-4-carboxylate (1 g.) and trimethylsilylacetamide (2.58 g.) in ethyl acetate (20 ml.) at -20° C. with stirring, and the mixed solution was stirred at -10° to -20° C. for 1.5 hours. To the resultant solution was added water (20 ml), and the solution was stirred at -20° C. After separating the ethyl acetate layer, the aqueous layer was extracted with ethyl acetate (20 ml.). The ethyl acetate layer and the extract were combined together, washed with 10% hydrochloric acid (20 ml.) twice, water (20 ml.) once, a 5% aqueous solution of sodium bicarbonate (20 ml.) three times, and an aqueous solution of sodium chloride (20 ml.) once in turn, dried, and then concentrated under reduced pressure. The residue was washed with diethyl ether (50 ml.) to give p-nitrobenzyl 7-{2-(2-formamido-4-thiazolyl)-2-methoxyiminoacetamido}-3-chloro-3-cephem-4-carboxylate (anti isomer, 1.27 g.), m.p. 135° to 145° C. (dec.).

Aufarbeitung

  1. temperaturecooling
  2. stirringthe mixture was stirred at the same temperature for 30 minutes
  3. customto prepare the activated acid solution
  4. stirringwith stirring
  5. stirringthe mixed solution was stirred at -10° to -20° C. for 1.5 hours
  6. stirringthe solution was stirred at -20° C
  7. customAfter separating the ethyl acetate layer
  8. extractionthe aqueous layer was extracted with ethyl acetate (20 ml.)
  9. washwashed with 10% hydrochloric acid (20 ml.) twice
  10. dry with materialwater (20 ml.) once, a 5% aqueous solution of sodium bicarbonate (20 ml.) three times, and an aqueous solution of sodium chloride (20 ml.) once in turn, dried
  11. concentrationconcentrated under reduced pressure
  12. washThe residue was washed with diethyl ether (50 ml.)

Quellen und Nachweise

ORD-Eintrag
ord-80d79d456cac4369908b4ae682a9d83e
Quelldatensatz
uspto-grants-1986_08
Patentnummer
US04604456

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