反応 #62773

反応方程式

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

収率 105.8%

溶媒

water

N,N-dimethylformamide

methylene chloride

反応条件

後処理

1. 1
   その他to give an activated acid solution
2. 2
   workup.STIRRINGwas stirred
3. 3
   その他for 30 minutes
4. 4
   その他at room temperature
5. 5
   温度cooled to -20° C
6. 6
   workup.ADDITIONTo this solution was added the activated acid solution
7. 7
   その他obtained above in one portion
8. 8
   workup.STIRRINGThe mixture was stirred for 30 minutes at -15° to -10° C.
9. 9
   抽出extracted with ethyl acetate
10. 10
    洗浄The extract was washed with water three times
11. 11
    乾燥dried over magnesium sulfate
12. 12
    その他evaporated under reduced pressure
13. 13
    その他The residue was triturated in diisopropyl ether

実験手順

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).

出典