Reacción #62773

Ecuación de reacción

2-(2-tritylaminothiazol-4-yl)-2-difluoromethoxyiminoacetic acid

diisopropylethylamine

benzhydryl 7-amino-3-chloromethyl-3-cephem-4-carboxylate

N-trimethylsilylacetamide

mesyl chloride

→

benzhydryl 7-[2-(2-tritylaminothiazol-4-yl)- 2-difluoromethoxyiminoacetamido]-3-chloromethyl-3-cephem-4-carboxylate

Rendimiento 105.8%

Disolventes

water

N,N-dimethylformamide

methylene chloride

Condiciones de reacción

Tratamiento posterior

1. 1
   Otroto give an activated acid solution
2. 2
   workup.STIRRINGwas stirred
3. 3
   Otrofor 30 minutes
4. 4
   Otroat room temperature
5. 5
   Temperaturacooled to -20° C
6. 6
   workup.ADDITIONTo this solution was added the activated acid solution
7. 7
   Otroobtained above in one portion
8. 8
   workup.STIRRINGThe mixture was stirred for 30 minutes at -15° to -10° C.
9. 9
   Extracciónextracted with ethyl acetate
10. 10
    LavadoThe extract was washed with water three times
11. 11
    Secadodried over magnesium sulfate
12. 12
    Otroevaporated under reduced pressure
13. 13
    OtroThe residue was triturated in diisopropyl ether

Procedimiento

A mixture of 2-(2-tritylaminothiazol-4-yl)-2-difluoromethoxyiminoacetic acid (syn isomer) (2.4 g) and diisopropylethylamine (1.29 g) in N,N-dimethylformamide (35 ml) was cooled to -30° C. and mesyl chloride (1.15 g) was added dropwise thereto. The mixture was stirred at -20° to -30° C. for 30 minutes to give an activated acid solution. On the other hand, a mixture of benzhydryl 7-amino-3-chloromethyl-3-cephem-4-carboxylate (2.18 g) and N-trimethylsilylacetamide (5.25 g) in methylene chloride (20 ml) was stirred to be a clear solution for 30 minutes at room temperature and then cooled to -20° C. To this solution was added the activated acid solution obtained above in one portion. The mixture was stirred for 30 minutes at -15° to -10° C., poured into water and extracted with ethyl acetate. The extract was washed with water three times, dried over magnesium sulfate and evaporated under reduced pressure. The residue was triturated in diisopropyl ether to give benzhydryl 7-[2-(2-tritylaminothiazol-4-yl)- 2-difluoromethoxyiminoacetamido]-3-chloromethyl-3-cephem-4-carboxylate (syn isomer) (4.64 g).

Fuente