تفاعل #65613

معادلة التفاعل

(2S,4S)-4-mercapto-2-(1-methyl-2-pyrrolidinylethylcarbamoyl)-1-(4-nitrobenzyloxycarbonyl)pyrrolidine bis(trifluoromethanesulfonate)

diisopropylethylamine

4-nitrobenzyl (1R,5R,6S)-6-[(1R)-1-hydroxyethyl]-1-methyl-2-oxo-1-carbapenam-3-carboxylate

diphenylphosphoryl chloride

diisopropylethylamine

→

title compound

(1R,5S,6S)-2-[(2S,4S)-2-(1,1-Dimethyl-2-pyrrolidinioethylcarbamoyl)pyrrolidin-4-ylthio]-6-[(1R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylate fluorosulfonate

المذيبات

acetonitrile

acetonitrile

ظروف التفاعل

المعالجة

1. 1
   أخرىthe solution was placed on an ice bath
2. 2
   workup.ADDITIONwere added dropwise to the solution
3. 3
   درجة الحرارةcooled temperature
4. 4
   workup.ADDITIONwere added dropwise to the mixture
5. 5
   درجة الحرارةcooled temperature for 5 hours
6. 6
   أخرىAt the end of this time, the solvent was removed by distillation under reduced pressure
7. 7
   workup.ADDITIONAn aqueous solution of sodium hydrogencarbonate was added to the residue, which
8. 8
   استخلاصwas then extracted with ethyl acetate
9. 9
   تجفيفThe organic layer was dried over anhydrous magnesium sulfate
10. 10
    أخرىThe solvent was removed by distillation under reduced pressure
11. 11
    غسيلFrom fractions eluted with a 1:2 by volume mixture of acetonitrile

الإجراء التجريبي

180 mg of 4-nitrobenzyl (1R,5R,6S)-6-[(1R)-1-hydroxyethyl]-1-methyl-2-oxo-1-carbapenam-3-carboxylate were dissolved in 2.3 ml of anhydrous acetonitrile, and the solution was placed on an ice bath. Maintaining the solution on the ice bath, 109 μl of diphenylphosphoryl chloride and 92 μl of diisopropylethylamine were added dropwise to the solution. The resulting mixture was then stirred for 1 hour at this ice-cooled temperature, after which, whilst still maintaining the reaction mixture on the ice bath, 313 μl of diisopropylethylamine and 1.9 ml of an anhydrous acetonitrile solution containing 440 mg of (2S,4S)-4-mercapto-2-(1-methyl-2-pyrrolidinylethylcarbamoyl)-1-(4-nitrobenzyloxycarbonyl)pyrrolidine bis(trifluoromethanesulfonate) [prepared as described in step (1) above] were added dropwise to the mixture. The mixture was then stirred at this ice-cooled temperature for 5 hours and allowed to stand for 2 days in a refrigerator. At the end of this time, the solvent was removed by distillation under reduced pressure. An aqueous solution of sodium hydrogencarbonate was added to the residue, which was then extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate. The solvent was removed by distillation under reduced pressure, and the resulting residue was subjected to Lobar column chromatography (Merck, LiChroprep Si60). From fractions eluted with a 1:2 by volume mixture of acetonitrile and methanol were obtained 65 mg of the title compound.

المصدر