Dicyclohexylcarbodiimide → HCID 178477376, Verbindung

HRID 426974Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 426974
[NH2:1][CH:2]1[C:24](=[O:25])[N:4]2[C:5]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])=[C:6]([CH:9]([S:11][C:12]3[NH:16][N:15]=[N:14][N:13]=3)[CH3:10])[CH2:7][S:8][C@H:3]12.C1(N=C=NC2CCCCC2)CCCCC1.[S:41]1[CH:45]=[CH:44][CH:43]=[C:42]1[S:46]([CH2:48][C:49](O)=[O:50])=[O:47]>C1C=CC=CC=1>[S:41]1[CH:45]=[CH:44][CH:43]=[C:42]1[S:46]([CH2:48][C:49]([NH:1][CH:2]1[C:24](=[O:25])[N:4]2[C:5]([C:17]([O:19][C:20]([CH3:21])([CH3:23])[CH3:22])=[O:18])=[C:6]([CH:9]([S:11][C:12]3[NH:13][N:14]=[N:15][N:16]=3)[CH3:10])[CH2:7][S:8][C@H:3]12)=[O:50])=[O:47]

Komponenten

5

Edukt 3

HCID 10868DicyclohexylcarbodiimideHCID 132357052-Thienylsulfinylacetic acidHCID 178477375HCID 178477375, Verbindung

Produkt 1

HCID 178477376HCID 178477376, VerbindungAusbeute 65,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 241BenzeneLösungsmittel

Reaktionsbedingungen

Temperatur
25 °C

Versuchsvorschrift

154 mg of t-butyl 7-amino-3-(1-methyl-1H-tetrazol-5-ylthiomethyl)-3-cephem-4-carboxylate and 83 mg of dicyclohexylcarbodiimide were dissolved in 5 ml of benzene, and 76 mg of 2-thienylsulfinylacetic acid ([α]D22° :+11.0°, C=1.00, ethanol) was added to the solution. This liquid reaction mixture was agitated at 25° C. for 2 hours. The mixture was filtered, made adsorbed on 2 g of silica gel and subjected to chromatography using benzene-ethyl acetate (50:50) on 20 g of silica gel to obtain 145 mg of t-butyl 7-(2-thienylsulfinylacetamido)-3-(1-methyl-1H-tetrazol-5-ylthiomethyl)-3-cephem-4-carboxylate. The so obtained ester was dissolved in 1 ml of trifluoroacetic acid, and the solution was agitated at 25° C. for 5 minutes. Then, the solution was added dropwise to 70 ml of ether. The resulting precipitate was collected and dissolved in 5% aqueous sodium bicarbonate solution to form 100 ml of a solution. Then, the solution was extracted with ethyl acetate, and the pH of the aqueous layer was adjusted to 2.0 and the aqueous layer was further extracted with ethyl acetate. The organic layer was dried and concentrated until the volume was reduced to 5 ml. The resulting residue was mixed with a 30% solution of sodium 2-ethylhexanoate in propanol, and ether was added to the mixture. The precipitated salt was collected, recrystallized from methanolether and dried under reduced pressure to obtain 51 mg of sodium 7-(2-thienylsulfinylacetamido)-3-(1-methyl-1H-tetrazol-5-ylthiomethyl)-3-cephem-4-carboxylate of the R form optically active in the sulfoxide. The NMR spectrum was found to be in agreement with that of the intended product. The bacterium-inhibiting activity of the so obtained compound was much superior to that of the product derived in the same manner by using 2-thienylsulfinylacetic acid having [α]D22° of -9.2° as the starting compound.

Aufarbeitung

  1. customThis liquid reaction mixture
  2. filtrationThe mixture was filtered

Quellen und Nachweise

ORD-Eintrag
ord-9ae30d3102b845729787074aaedcf9b5
Quelldatensatz
uspto-grants-1979_10
Patentnummer
US04172197

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