Реакция #449194

Уравнение реакции

diisopropylethylamine

(2S,4S)-4-mercapto-2-(4-methyl-1-piperazinylcarbonyl)-1-methylpyrrolidine bis(trifluoromethanesulfonate)

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

chloride

diisopropylethylamine

→

title compound

Выход 50.0%

4-Nitrobenzyl (1R,5S,6S)-2-[(2S,4S)-2-(4-methyl-1-piperazinylcarbonyl)-1-methylpyrrolidin-4-ylthio]-6-[(1R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylate

Выход 50.0%

Растворители

acetonitrile

acetonitrile

Условия реакции

Обработка

1. 1
   Температураcooling
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
   ДругоеAt the end of this time, the solvent was removed by distillation under reduced pressure
5. 5
   Другоеthe residue was purified by chromatography through a Lobar column (Merck, LiChroprep RP-8, size B)
6. 6
   ПромывкаThe column was successively eluted with 65% by volume aqueous methanol and with 70% by volume aqueous methanol
7. 7
   workup.ADDITIONThose fractions containing the title compound
8. 8
   Концентрированиеconcentrated by evaporation under reduced pressure

Методика

540 μl of diphenylphosophoryl chloride and 470 μl of diisopropylethylamine were added dropwise, whilst ice-cooling, to a solution of 920 mg of 4-nitro-benzyl (1R,5R,6S)-6-[(1R)-1-hydroxyethyl]-1-methyl-2-oxo-1-carbapenam-3-carboxylate in 10 ml of dry acetonitrile, and the resulting mixture was stirred at the same temperature for 1 hour. 1400 μl of diisopropylethylamine and a solution of 1350 mg of (2S,4S)-4-mercapto-2-(4-methyl-1-piperazinylcarbonyl)-1-methylpyrrolidine bis(trifluoromethanesulfonate) (prepared as described in Preparation 51) in 5 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 purified by chromatography through a Lobar column (Merck, LiChroprep RP-8, size B). The column was successively eluted with 65% by volume aqueous methanol and with 70% by volume aqueous methanol. Those fractions containing the title compound were combined and concentrated by evaporation under reduced pressure, to give 730 mg of the title compound, as a powder.

Источник