Réaction #62773

Équation de réaction

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

Rendement 105.8%

Solvants

water

N,N-dimethylformamide

methylene chloride

Conditions de réaction

Traitement

1. 1
   Autreto give an activated acid solution
2. 2
   workup.STIRRINGwas stirred
3. 3
   Autrefor 30 minutes
4. 4
   Autreat room temperature
5. 5
   Températurecooled to -20° C
6. 6
   workup.ADDITIONTo this solution was added the activated acid solution
7. 7
   Autreobtained above in one portion
8. 8
   workup.STIRRINGThe mixture was stirred for 30 minutes at -15° to -10° C.
9. 9
   Extractionextracted with ethyl acetate
10. 10
    LavageThe extract was washed with water three times
11. 11
    Séchagedried over magnesium sulfate
12. 12
    Autreevaporated under reduced pressure
13. 13
    AutreThe residue was triturated in diisopropyl ether

Mode opératoire

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).

Source