Reaktion #56300

Reaktionsgleichung

triethylamine

N-tosylphthalimide

sodium chloride

sodium 7β-(t-butoxycarbonyl)amino-3-hydroxymethyl-3-cephem-4-carboxylate

→

7β-(t-butoxycarbonyl)amino-3-[2-(N-tosylcarbamoyl)benzoyloxy]methyl-3-cephem-4-carboxylic acid

Ausbeute 42.2%

Lösungsmittel

toluene

n-Hexane

water

N,N-dimethylformamide

water

ethyl acetate

acetic acid

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturcooling
2. 2
   Filtrationthe resultant precipitate is collected by filtration
3. 3
   Waschenwashed with toluene
4. 4
   Sonstigedried
5. 5
   SonstigeThe powder thus obtained
6. 6
   FiltrationThe resultant precipitate is collected by filtration
7. 7
   Waschenwashed with water
8. 8
   SonstigeThe cake thus obtained
9. 9
   SonstigeAfter separation
10. 10
    Waschenthe ethyl acetate layer is washed with water and water (10 ml)
11. 11
    workup.ADDITIONis added
12. 12
    workup.ADDITIONSodium hydrogen carbonate is added
13. 13
    SonstigeAfter separation
14. 14
    Waschenthe aqueous layer is washed with ethyl acetate and ethyl acetate (20 ml)
15. 15
    workup.ADDITIONis added
16. 16
    workup.ADDITIONTo the mixture, diluted phosphoric acid is added
17. 17
    SonstigeAfter separation
18. 18
    Waschenthe ethyl acetate layer is washed with water
19. 19
    Trocknendried over anhydrous sodium sulfate
20. 20
    Einengenconcentrated
21. 21
    workup.ADDITIONTo the residue, ether is added
22. 22
    workup.STIRRINGunder stirring
23. 23
    Filtrationthe resultant insolubles are filtered off
24. 24
    EinengenThe filtrate is concentrated under reduced pressure and carbon tetrachloride
25. 25
    workup.ADDITIONis added
26. 26
    FiltrationThe resultant precipitate is collected by filtration and dried phosphorus pentoxide

Vorschrift

In N,N-dimethylformamide (8 ml), is dissolved sodium 7β-(t-butoxycarbonyl)amino-3-hydroxymethyl-3-cephem-4-carboxylate (1.60 g), followed by addition of triethylamine (3 ml) and N-tosylphthalimide(1.80 g) under ice-cooling. The mixture is stirred for one hour and then poured into toluene (300 ml). n-Hexane (200 ml) is added and the resultant precipitate is collected by filtration, washed with toluene and dried. The powder thus obtained is dissolved in water (50 ml). The solution is adjusted to pH 3.7 with acetic acid and a saturated aqueous solution of sodium chloride (50 ml) is added. The resultant precipitate is collected by filtration and washed with water. The cake thus obtained is added to a mixed solution of ethyl acetate (30 ml) and water (10 ml). After separation, the ethyl acetate layer is washed with water and water (10 ml) is added. Sodium hydrogen carbonate is added to adjust to pH 6.8. After separation, the aqueous layer is washed with ethyl acetate and ethyl acetate (20 ml) is added. To the mixture, diluted phosphoric acid is added to adjust to pH 4.0. After separation, the ethyl acetate layer is washed with water, dried over anhydrous sodium sulfate and concentrated. To the residue, ether is added under stirring and the resultant insolubles are filtered off. The filtrate is concentrated under reduced pressure and carbon tetrachloride is added. The resultant precipitate is collected by filtration and dried phosphorus pentoxide. The procedure provides 7β-(t-butoxycarbonyl)amino-3-[2-(N-tosylcarbamoyl)benzoyloxy]methyl-3-cephem-4-carboxylic acid (1.21 g).

Quelle