تفاعل #449176

معادلة التفاعل

(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

المردود 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

المردود 21.6%

المذيبات

acetonitrile

diisopropylethylamine

acetonitrile

diisopropylethylamine

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةcooling
2. 2
   workup.WAITto stand overnight at the same temperature
3. 3
   تركيزThe reaction mixture was then concentrated by evaporation under reduced pressure
4. 4
   workup.ADDITIONthe concentrate was diluted with ethyl acetate
5. 5
   غسيلThe diluted solution was washed, in turn, with water and with an aqueous solution of sodium chloride
6. 6
   تجفيفafter which it was dried over anhydrous magnesium sulfate
7. 7
   أخرىThe solvent was then removed by distillation under reduced pressure
8. 8
   أخرىthe 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
    تركيزconcentrated by evaporation under reduced pressure

الإجراء التجريبي

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.

المصدر