Reacción #214276

Ecuación de reacción

2-methanesulfonamidothiazol-5-ylacetic acid

sodium bicarbonate

sodium bicarbonate

3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-7-amino-3-cephem-4-carboxylic acid

phosphorus pentachloride

→

3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-7-(2-methanesulfonamidothiazol-5-yl)acetamido-3-cephem-4-carboxylic acid

Rendimiento 45.8%

Disolventes

diethyl ether

methylene chloride

acetone

acetone

water

n-hexane

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturacooling
2. 2
   workup.STIRRINGthe mixture was stirred for 30 minutes at the same temperature
3. 3
   Lavadothe precipitated crystals were washed by decantation three times
4. 4
   workup.ADDITIONThus obtained crystals were gradually added to a solution, which
5. 5
   Otrois prepared
6. 6
   Temperaturaby cooling it at 0° to 5° C.
7. 7
   Temperaturaunder ice-cooling
8. 8
   workup.STIRRINGstirring while the mixture
9. 9
   workup.STIRRINGThe mixture was further stirred for 40 minutes at about the same pH and temperature
10. 10
    Otrowas removed
11. 11
    Lavadoby washing the reaction mixture with benzene
12. 12
    Filtraciónfiltered
13. 13
    Temperaturacooling
14. 14
    OtroThe ethyl acetate layer was separated from the mixture
15. 15
    Extracciónthe remaining aqueous layer was extracted twice with ethyl acetate (70 ml.)
16. 16
    Lavadowashed with water
17. 17
    Secadoa saturated sodium chloride aqueous solution in turn and then dried over magnesium sulfate
18. 18
    workup.DISTILLATIONThe solvent was distilled off from the ethyl acetate layer
19. 19
    Otrothe resulting yellow powder was dried

Procedimiento

To a mixture of 2-methanesulfonamidothiazol-5-ylacetic acid (1.65 g.), dried methylene chloride (40 ml.) and diethyl ether (4 ml.) was added phosphorus pentachloride (3.5 g.) under ice-cooling and stirring and the mixture was stirred for 30 minutes at the same temperature. To the mixture was added n-hexane, and the precipitated crystals were washed by decantation three times. Thus obtained crystals were gradually added to a solution, which is prepared by adding sodium bicarbonate (2.15 g.) to a suspension of 3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-7-amino-3-cephem-4-carboxylic acid (2.1 g.) in a mixture of acetone (25 ml.) and water (25 ml.) and then by cooling it at 0° to 5° C., under ice-cooling and stirring while the mixture was kept to pH 7.5 to 8 with a saturated sodium bicarbonate aqueous solution. The mixture was further stirred for 40 minutes at about the same pH and temperature. After the reaction, acetone was removed by washing the reaction mixture with benzene. The aqueous layer was adjusted to pH 5 with 5% hydrochloric acid and filtered. To the aqueous filtrate was overlayed ethyl acetate, and the mixture was gradually adjusted to pH 2 with 5% hydrochloric acid under ice-cooling. The ethyl acetate layer was separated from the mixture, and the remaining aqueous layer was extracted twice with ethyl acetate (70 ml.). The ethyl acetate layers were combined together, washed with water and a saturated sodium chloride aqueous solution in turn and then dried over magnesium sulfate. The solvent was distilled off from the ethyl acetate layer, and the resulting yellow powder was dried to give a mixture (1.6 g.) of 3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-7-(2-methanesulfonamidothiazol-5-yl)acetamido-3-cephem-4-carboxylic acid (hereinafter referred to Amino compound) and 3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-7-(2-methanesulfonimido-2,3-dihydrothiazol-5-yl)acetamido-3-cephem-4-carboxylic acid (hereinafter referred to Imino compound).

Fuente