Reaktion #4867

Reaktionsgleichung

(Z)-2-(2-tritylaminothiazol-4-yl)-2-[(2-pyrrolidon-3-yl)oxyimino]acetic acid

7β-amino-3-(1-pyridinio-methyl)-3-cephem-4-carboxylate

dihydrochloride

N,O-bis(trimethylsilyl)acetamide

oxalyl chloride

→

7β-{(Z)-2-(2-aminothiazol-4-yl)-2-[(2-pyrrolidon-3-yl)oxyimino]acetamido}-3-(1-pyridiniomethyl)-3-cephem-4-carboxylate

Lösungsmittel

chloroform

triethylamine

chloroform

water

chloroform

dimethylformamide

chloroform

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONis added
2. 2
   Sonstigeat -30° to -35° C.
3. 3
   workup.STIRRINGthe mixture is further stirred at the same temperature for 5 minutes
4. 4
   Sonstigeis prepared
5. 5
   workup.DISSOLUTIONto dissolve
6. 6
   workup.ADDITION) is added
7. 7
   Sonstigeat -35° to -30° C.
8. 8
   workup.STIRRINGthe mixture is stirred at the same temperature for 10 minutes and at -30° to -10° C. for one hour
9. 9
   EinengenThe mixture is concentrated to dryness under reduced pressure
10. 10
    workup.ADDITION60 ml of 80% aqueous formic acid are added to the residue
11. 11
    workup.STIRRINGthe aqueous mixture is stirred at room temperature for one hour
12. 12
    workup.ADDITION50 ml of water are added
13. 13
    FiltrationThen, insoluble materials are filtered off
14. 14
    Waschenthe filtrate is washed with ethyl acetate
15. 15
    Einengenconcentrated to dryness under reduced pressure
16. 16
    SonstigeThe residue thus obtained
17. 17
    Sonstigechromatographed on a column of non-ionic polymer resin Diaion
18. 18
    WaschenThe column is washed with water
19. 19
    Waschenfollowed by elution with 20% methanol
20. 20
    workup.ADDITIONThe fractions containing the cephalosporin compound
21. 21
    Sonstigeare collected
22. 22
    Einengenconcentrated to dryness under reduced pressure
23. 23
    workup.ADDITIONAcetone is added to the residue
24. 24
    Sonstigethus obtained
25. 25
    Filtrationthe resulting powder is collected by filtration

Vorschrift

0.57 g of oxalyl chloride is added at -5° to 0° C. to 15 ml of chloroform containing 0.35 g of dimethylformamide, and the mixture is stirred at the same temperature for 15 minutes. A mixture of 1.54 g of (Z)-2-(2-tritylaminothiazol-4-yl)-2-[(2-pyrrolidon-3-yl)oxyimino]acetic acid, 0.3 g of triethylamine and 15 ml of chloroform is added to said mixture at -30° to -35° C., and the mixture is further stirred at the same temperature for 5 minutes. Then, a solution of 7β-amino-3-(1-pyridinio-methyl)-3-cephem-4-carboxylate in chloroform (said solution is prepared by suspending 1.82 g of the dihydrochloride of said cephem compound in 10 ml of chloroform and adding 4 ml of N,O-bis(trimethylsilyl)acetamide thereto to dissolve said salt therein) is added to said mixture at -35° to -30° C., and the mixture is stirred at the same temperature for 10 minutes and at -30° to -10° C. for one hour. The mixture is concentrated to dryness under reduced pressure. 60 ml of 80% aqueous formic acid are added to the residue, and the aqueous mixture is stirred at room temperature for one hour. 50 ml of water are added to said aqueous mixture. Then, insoluble materials are filtered off, and the filtrate is washed with ethyl acetate and concentrated to dryness under reduced pressure. The residue thus obtained is dissolved in water and chromatographed on a column of non-ionic polymer resin Diaion HP-20 (registered trade mark, manufactured by Mitsubishi Chemical Industries Ltd., Japan). The column is washed with water, followed by elution with 20% methanol. The fractions containing the cephalosporin compound are collected and concentrated to dryness under reduced pressure. Acetone is added to the residue thus obtained, and the resulting powder is collected by filtration. 0.84 g of 7β-{(Z)-2-(2-aminothiazol-4-yl)-2-[(2-pyrrolidon-3-yl)oxyimino]acetamido}-3-(1-pyridiniomethyl)-3-cephem-4-carboxylate is obtained.

Quelle