Reacción #56300

Ecuación de reacción

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

Rendimiento 42.2%

Disolventes

toluene

n-Hexane

water

N,N-dimethylformamide

water

ethyl acetate

acetic acid

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturacooling
2. 2
   Filtraciónthe resultant precipitate is collected by filtration
3. 3
   Lavadowashed with toluene
4. 4
   Otrodried
5. 5
   OtroThe powder thus obtained
6. 6
   FiltraciónThe resultant precipitate is collected by filtration
7. 7
   Lavadowashed with water
8. 8
   OtroThe cake thus obtained
9. 9
   OtroAfter separation
10. 10
    Lavadothe 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
    OtroAfter separation
14. 14
    Lavadothe 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
    OtroAfter separation
18. 18
    Lavadothe ethyl acetate layer is washed with water
19. 19
    Secadodried over anhydrous sodium sulfate
20. 20
    Concentraciónconcentrated
21. 21
    workup.ADDITIONTo the residue, ether is added
22. 22
    workup.STIRRINGunder stirring
23. 23
    Filtraciónthe resultant insolubles are filtered off
24. 24
    ConcentraciónThe filtrate is concentrated under reduced pressure and carbon tetrachloride
25. 25
    workup.ADDITIONis added
26. 26
    FiltraciónThe resultant precipitate is collected by filtration and dried phosphorus pentoxide

Procedimiento

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).

Fuente