反応 #552523

反応方程式

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

収率 39.3%

溶媒

water

acetonitrile

acetonitrile

反応条件

後処理

1. 1
   workup.STIRRINGThe mixture is stirred at the same temperature for 1.5 hour
2. 2
   濃縮The mixture is concentrated under reduced pressure
3. 3
   その他to remove acetonitrile
4. 4
   抽出The residue is extracted with ethyl acetate
5. 5
   洗浄the extract is washed with water
6. 6
   その他dried
7. 7
   その他evaporated to dryness under reduced pressure
8. 8
   その他The residue is purified by silica gel column chromatography (eluent, chloroform:methanol=99:1)

実験手順

(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.

出典