Reaction #62773

Reaction equation

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

Yield 105.8%

Solvents

water

N,N-dimethylformamide

methylene chloride

Conditions

Workup

1. 1
   Otherto give an activated acid solution
2. 2
   workup.STIRRINGwas stirred
3. 3
   Otherfor 30 minutes
4. 4
   Otherat room temperature
5. 5
   Temperaturecooled to -20° C
6. 6
   workup.ADDITIONTo this solution was added the activated acid solution
7. 7
   Otherobtained 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
    WashThe extract was washed with water three times
11. 11
    Dryingdried over magnesium sulfate
12. 12
    Otherevaporated under reduced pressure
13. 13
    OtherThe residue was triturated in diisopropyl ether

Procedure

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