반응 #62773

반응 방정식

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

수율 105.8%

용매

water

N,N-dimethylformamide

methylene chloride

반응 조건

후처리

1. 1
   기타to give an activated acid solution
2. 2
   workup.STIRRINGwas stirred
3. 3
   기타for 30 minutes
4. 4
   기타at room temperature
5. 5
   온도cooled to -20° C
6. 6
   workup.ADDITIONTo this solution was added the activated acid solution
7. 7
   기타obtained above in one portion
8. 8
   workup.STIRRINGThe mixture was stirred for 30 minutes at -15° to -10° C.
9. 9
   추출extracted with ethyl acetate
10. 10
    세척The extract was washed with water three times
11. 11
    건조dried over magnesium sulfate
12. 12
    기타evaporated under reduced pressure
13. 13
    기타The residue was triturated in diisopropyl ether

실험 절차

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).

출처