تفاعل #449198

معادلة التفاعل

diisopropylethyl-amine

(2S,4S)-4-mercapto-2-[4-(2-carbamoyloxyethyl)-1-piperazinylcarbonyl]-1-(4-nitrobenzyloxycarbonyl)pyrrolidine trifluoromethane-sulfonate

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

diphenylphosphoryl chloride

diisopropylethylamine

→

title compound

المردود 28.6%

4-Nitrobenzyl (1R,5S,6S)-2-{(2S,4S)-2-[4-(2-carbamoyloxyethyl)-1-piperazinylcarbonyl]-1-(4-nitro-benzyloxycarbonyl)pyrrolidin-4-ylthio}-6-[(1R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylate

المردود 28.6%

المذيبات

acetonitrile

acetonitrile

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةcooling
2. 2
   workup.STIRRINGthe resulting mixture was stirred at the same temperature for 2 hours
3. 3
   workup.WAITto stand overnight in a refrigerator
4. 4
   أخرىAt the end of this time, the solvent was removed by distillation under reduced pressure
5. 5
   workup.ADDITIONthe residue was mixed with an aqueous solution of sodium hydrogencarbonate
6. 6
   استخلاصThe mixture was then extracted with ethyl acetate
7. 7
   تجفيفthe extract was dried over anhydrous magnesium sulfate
8. 8
   أخرىThe solvent was then removed from the
9. 9
   استخلاصextract by distillation under reduced pressure
10. 10
    أخرىthe resulting residue was purified by chromatography through a Lobar column (Merck, LiChroprep Si60, size B)
11. 11
    workup.ADDITIONby volume mixture of ethyl acetate and methanol as the eluent

الإجراء التجريبي

91 μl of diphenylphosphoryl chloride and 77 μl of diisopropylethylamine were added dropwise, whilst ice-cooling, to a solution of 152 mg of 4-nitrobenzyl (1R,5R,6S)-6-[(1R)-1-hydroxyethyl]-1-methyl-2-oxo-1-carbapenam-3-carboxylate in 2.0 ml of dry acetonitrile, and the resulting mixture was stirred at the same temperature for 1 hour. 176 μl of diisopropylethyl-amine and a solution of 318 mg of (2S,4S)-4-mercapto-2-[4-(2-carbamoyloxyethyl)-1-piperazinylcarbonyl]-1-(4-nitrobenzyloxycarbonyl)pyrrolidine trifluoromethane-sulfonate (prepared as described in Preparation 53) in 2.0 ml of dry acetonitrile were then simultaneously added dropwise to the mixture, whilst ice-cooling, and the resulting mixture was stirred at the same temperature for 2 hours, after which it was allowed to stand overnight in a refrigerator. At the end of this time, the solvent was removed by distillation under reduced pressure, and the residue was mixed with an aqueous solution of sodium hydrogencarbonate. The mixture was then extracted with ethyl acetate, and the extract was dried over anhydrous magnesium sulfate. The solvent was then removed from the extract by distillation under reduced pressure, and the resulting residue was purified by chromatography through a Lobar column (Merck, LiChroprep Si60, size B), using a 5:1 by volume mixture of ethyl acetate and methanol as the eluent to give 99 mg of the title compound, as a powder.

المصدر