Isopropanol → 3-[(8-Amino-6-tetrazolo[1,5-b]pyridazinyl)-thiomethyl]-7-(4-chloro-3-oxobutyramido)-3-cephem-4-carboxylic acid

HRID 1065850

Reaktionsgleichung

Reaktionsgleichung von HRID 1065850
[NH2:1][CH:2]1[C:24](=[O:25])[N:4]2[C:5]([C:21]([OH:23])=[O:22])=[C:6]([CH2:9][S:10][C:11]3[CH:12]=[C:13]([NH2:20])[C:14]4[N:15]([N:17]=[N:18][N:19]=4)[N:16]=3)[CH2:7][S:8][C@H:3]12.C/C(/O[Si](C)(C)C)=N\[Si](C)(C)C.[Cl:38][CH2:39][C:40](=[O:45])[CH2:41][C:42](Cl)=[O:43].C(O)(C)C>CN(C)C=O.C(Cl)Cl>[NH2:20][C:13]1[C:14]2[N:15]([N:17]=[N:18][N:19]=2)[N:16]=[C:11]([S:10][CH2:9][C:6]2[CH2:7][S:8][C@@H:3]3[CH:2]([NH:1][C:42](=[O:43])[CH2:41][C:40](=[O:45])[CH2:39][Cl:38])[C:24](=[O:25])[N:4]3[C:5]=2[C:21]([OH:23])=[O:22])[CH:12]=1

Komponenten

7

Edukt 4

HCID 3776IsopropanolHCID 30162624-Chloro-3-oxobutyryl chlorideHCID 6913588N,O-bis(trimethylsilyl)acetamideHCID 1317127277-Amino-3-[(8-amino-6-tetrazolo[1,5-b]pyridazinyl)thiomethyl]-3-cephem-4-carboxylic acid

Produkt 1

HCID 1317127263-[(8-Amino-6-tetrazolo[1,5-b]pyridazinyl)-thiomethyl]-7-(4-chloro-3-oxobutyramido)-3-cephem-4-carboxylic acidAusbeute 92,2 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

7-Amino-3-[(8-amino-6-tetrazolo[1,5-b]pyridazinyl)thiomethyl]-3-cephem-4-carboxylic acid (3.8 g; 0.01 mole) was suspended in anhydrous N,N-dimethylformamide (50 ml) and N,O-bis(trimethylsilyl)acetamide (8.13 g; 0.04 mole) was added. After 2 hours of stirring at room temperature almost all the starting material was dissolved. A solution of 4-chloroacetoacetyl chloride (2.35 g; approximately 0.015 mole) in anhydrous methylene chloride (20 cc) was dropped into the cooled mixture (at -30° C.). The mixture was stirred at -30° C. for 2 hours and allowed to come to room temperature within an additional hour, after which time isopropanol (40 ml) was added, in order to decompose the silylated compounds. The solvents were evaporated under reduced pressure and the oily residue was partitioned between water and ethyl acetate. The organic layer was separated, washed with aqueous sodium chloride solution, concentrated to a small volume under reduced pressure, and diethyl ether was added to complete the precipitation. The solid was collected by filtration, washed with fresh ether and dried under vacuum, thus giving 4.6 g of the title compound, which was used in the following step without further purification.

Aufarbeitung

  1. dissolutionwas dissolved
  2. stirringThe mixture was stirred at -30° C. for 2 hours
  3. waitto come to room temperature within an additional hour
  4. customThe solvents were evaporated under reduced pressure
  5. customthe oily residue was partitioned between water and ethyl acetate
  6. customThe organic layer was separated
  7. washwashed with aqueous sodium chloride solution
  8. concentrationconcentrated to a small volume under reduced pressure, and diethyl ether
  9. additionwas added
  10. customthe precipitation
  11. filtrationThe solid was collected by filtration
  12. washwashed with fresh ether
  13. customdried under vacuum

Quellen und Nachweise

ORD-Eintrag
ord-a999cad4592840c4bba4ea16d2397ac4
Quelldatensatz
uspto-grants-1982_05
Patentnummer
US04331666

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