Реакция #449176

Уравнение реакции

(2S, 4S)-4-mercapto-2-[4-(N-4-nitrobenzyloxycarbonylacetimidoyl)piperazin-1-ylcarbonyl]-1-(4-nitrobenzyloxycarbonyl)pyrrolidine trifluoromethanesulfonate

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

diphenylphosphoryl chloride

→

title compound

Выход 21.6%

4-Nitrobenzyl (1R,5S,6S)-2-[(2S,4S)-2-[4-(N-4-nitrobenzyloxycarbonylacetimidoyl)piperazin-1-ylcarbonyl]-1-(4-nitrobenzyloxycarbonyl)pyrrolidin-4-ylthio]-6-[(1R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylate

Выход 21.6%

Растворители

acetonitrile

diisopropylethylamine

acetonitrile

diisopropylethylamine

Условия реакции

Обработка

1. 1
   Температураcooling
2. 2
   workup.WAITto stand overnight at the same temperature
3. 3
   КонцентрированиеThe reaction mixture was then concentrated by evaporation under reduced pressure
4. 4
   workup.ADDITIONthe concentrate was diluted with ethyl acetate
5. 5
   ПромывкаThe diluted solution was washed, in turn, with water and with an aqueous solution of sodium chloride
6. 6
   Сушкаafter which it was dried over anhydrous magnesium sulfate
7. 7
   ДругоеThe solvent was then removed by distillation under reduced pressure
8. 8
   Другоеthe resulting residue was purified by column chromatography through 100 ml of silica gel 60 (Merck Art No. 9385)
9. 9
   workup.ADDITIONby volume mixture of ethyl acetate, methylene chloride and methanol as the eluent
10. 10
    workup.ADDITIONThose fractions containing the title compound
11. 11
    Концентрированиеconcentrated by evaporation under reduced pressure

Методика

127 μl of diphenylphosphoryl chloride and 108 μl of diisopropylethylamine were added dropwise, whilst ice-cooling, to a solution of 210 mg of 4-nitrobenzyl (1R, 5R, 6S)-6-[(1R)-1-hydroxyethyl]-1-methyl-2-oxo-1-carbapenam-3-carboxylate in 2.6 ml of dry acetonitrile, and the resulting mixture was stirred at the same temperature for 1 hour. At the end of this time, a solution of 450 mg of (2S, 4S)-4-mercapto-2-[4-(N-4-nitrobenzyloxycarbonylacetimidoyl)piperazin-1-ylcarbonyl]-1-(4-nitrobenzyloxycarbonyl)pyrrolidine trifluoromethanesulfonate (prepared as described in Preparation 1) in 2.4 ml of dry acetonitrile and 274 μl of diisopropylethylamine were simultaneously added dropwise to the mixture, whilst ice-cooling, and the mixture was allowed to stand overnight at the same temperature. The reaction mixture was then concentrated by evaporation under reduced pressure, and the concentrate was diluted with ethyl acetate. The diluted solution was washed, in turn, with water and with an aqueous solution of sodium chloride, after which it was dried over anhydrous magnesium sulfate. The solvent was then removed by distillation under reduced pressure, and the resulting residue was purified by column chromatography through 100 ml of silica gel 60 (Merck Art No. 9385), using a 10:5:2 by volume mixture of ethyl acetate, methylene chloride and methanol as the eluent. Those fractions containing the title compound were combined and concentrated by evaporation under reduced pressure, to give 120 mg of the title compound, as an amorphous solid.

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