Реакция #552523

Уравнение реакции

diisopropylethylamine

diphenylphosphoryl chloride

(1R, 5R, 6S)-6-[(1R)-1-Hydroxyethyl]-1-methyl-2-oxocarbapenam-3-carboxylic acid 4-nitrobenzyl ester

(3R)-3-mercaptopyrrolidine-2-thione

diisopropylethylamine

→

(1R, 5S, 6S)-2-[(3R)-pyrrolidine-2-thion-3-ylthio]-6-[(1R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylic acid 4-nitrobenzyl ester

Выход 39.3%

Растворители

water

acetonitrile

acetonitrile

Условия реакции

Обработка

1. 1
   workup.STIRRINGThe mixture is stirred at the same temperature for 1.5 hour
2. 2
   КонцентрированиеThe mixture is concentrated under reduced pressure
3. 3
   Другоеto remove acetonitrile
4. 4
   ЭкстракцияThe residue is extracted with ethyl acetate
5. 5
   Промывкаthe extract is washed with water
6. 6
   Другоеdried
7. 7
   Другоеevaporated to dryness under reduced pressure
8. 8
   ДругоеThe residue is purified by silica gel column chromatography (eluent, chloroform:methanol=99:1)

Методика

(1R, 5R, 6S)-6-[(1R)-1-Hydroxyethyl]-1-methyl-2-oxocarbapenam-3-carboxylic acid 4-nitrobenzyl ester (8.3 g) is dissolved in anhydrous acetonitrile (50 ml), and thereto are added dropwise diisopropylethylamine (4 ml) and diphenylphosphoryl chloride (4.8 ml) in this order under nitrogen gas below 0° C. After stirring the mixture at the same temperature for 30 minutes, a solution of (3R)-3-mercaptopyrrolidine-2-thione (4 g) and diisopropylethylamine (4 ml) in anhydrous acetonitrile (50 ml) is added dropwise to the reaction mixture below -15° C. The mixture is stirred at the same temperature for 1.5 hour, and water (50 ml) is added to the reaction mixture. The mixture is concentrated under reduced pressure to remove acetonitrile. The residue is extracted with ethyl acetate, and the extract is washed with water, dried and evaporated to dryness under reduced pressure. The residue is purified by silica gel column chromatography (eluent, chloroform:methanol=99:1) to give (1R, 5S, 6S)-2-[(3R)-pyrrolidine-2-thion-3-ylthio]-6-[(1R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylic acid 4-nitrobenzyl ester (4.3 g) as an amorphous powder.

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