Reacción #551576

Ecuación de reacción

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

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

1-hydroxybenzotriazole

dicyclohexylcarbodiimide

→

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

Disolventes

tetrahydrofuran

N,N-dimethylacetamide

water

triethylamine

ethyl acetate

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturaunder ice-cooling
2. 2
   workup.STIRRINGThe mixture is stirred at room temperature for 2 hours
3. 3
   workup.ADDITIONare added
4. 4
   workup.STIRRINGThe mixture is stirred at 5° to 10° C. for one hour and further at room temperature for 15 hours
5. 5
   workup.ADDITIONare added
6. 6
   workup.STIRRINGThe mixture is stirred for 10 minutes
7. 7
   Filtracióninsoluble materials are filtered off
8. 8
   OtroThe aqueous layer is collected from the filtrate
9. 9
   OtroThe oily material thus obtained
10. 10
    Extracciónis extracted with a mixture of ethyl acetate and tetrahydrofuran (10:3)
11. 11
    LavadoThe extract is washed with water
12. 12
    Otrodried
13. 13
    Concentraciónconcentrated under reduced pressure
14. 14
    Otroto remove solvent
15. 15
    OtroThe residue is triturated with ethyl acetate
16. 16
    Otrothus-precipitated powder
17. 17
    Filtraciónis collected by filtration
18. 18
    workup.DISSOLUTIONThe powder is dissolved in 100 ml of tetrahydrofuran
19. 19
    Temperaturawith heating
20. 20
    workup.ADDITION250 ml of ethyl acetate are added
21. 21
    TemperaturaAfter cooling
22. 22
    Otrocrystalline precipitates
23. 23
    Filtraciónare collected by filtration

Procedimiento

11.5 g of (Z)-2-(2-tritylaminothiazol-4-yl)-2-[((3RS)-2-pyrrolidon-3-yl)oxyimino]acetic acid are suspended in 150 ml of tetrahydrofuran, and 3.2 g of 1-hydroxybenzotriazole and 4.7 g of dicyclohexylcarbodiimide are added thereto under ice-cooling and stirring. The mixture is stirred at room temperature for 2 hours. The mixture is cooled with ice, and 4.9 g of 7β-amino-3-(1-amino-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid dissolved in a mixture of 50 ml of N,N-dimethylacetamide, 2 ml of water and 3 g of triethylamine are added thereto. The mixture is stirred at 5° to 10° C. for one hour and further at room temperature for 15 hours. The reaction mixture is poured into 750 ml of ice-water, and 250 ml of ethyl acetate are added thereto. The mixture is stirred for 10 minutes and insoluble materials are filtered off. The aqueous layer is collected from the filtrate and is adjusted to pH 3 with 10% hydrochloric acid. The oily material thus obtained is extracted with a mixture of ethyl acetate and tetrahydrofuran (10:3). The extract is washed with water, dried and concentrated under reduced pressure to remove solvent. The residue is triturated with ethyl acetate and thus-precipitated powder is collected by filtration. The powder is dissolved in 100 ml of tetrahydrofuran with heating, and 250 ml of ethyl acetate are added thereto. After cooling, crystalline precipitates are collected by filtration. 4.8 g of 7β-{(Z)-2-tritylaminothiazol-4-yl)- 2-[((3RS)-2-pyrrolidon-3-yl)oxyimino]acetamido}-3-(1-amino-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid are obtained as colorless crystals.

Fuente