Реакция #552520

Уравнение реакции

phosphate

(4R)-N-methyl-4- mercaptopyrrolidine-2-thione

diisopropylethylamine

diisopropylethylamine

diphenylphosphoryl chloride

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

→

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

Выход 68.7%

Растворители

acetonitrile

acetonitrile

Условия реакции

Обработка

1. 1
   workup.STIRRINGAfter stirring the mixture at 0° C. for 1.5 hour
2. 2
   ДругоеThe precipitated crystal is separated by filtration
3. 3
   workup.DISSOLUTIONdissolved in a mixture of chloroform (2 liters) and tetrahydrofuran (1 liter)
4. 4
   Промывкаthe solution is washed with water
5. 5
   Другоеdried
6. 6
   Концентрированиеconcentrated to dryness under reduced pressure
7. 7
   ДругоеThe residue is crystallized from diethyl ether

Методика

(1R, 5R, 6S)-6-[(1R)-1-Hydroxyethyl]-1-methyl-2- oxocarbapenam-3-carboxylic acid 4-nitrobenzyl ester (25.2 g) is dissolved in anhydrous acetonitrile (173 ml), and thereto are added dropwise diisopropylethylamine (13 ml) and diphenylphosphoryl chloride (15.5 ml) in this order under nitrogen gas below 0° C. After stirring the mixture at the same temperature for 30 minutes, a solution of (4R)-N-methyl-4- mercaptopyrrolidine-2-thione (13 g) and diisopropylethylamine (11.5 g) in anhydrous acetonitrile (173 ml) is added dropwise to the reaction mixture below -5° C. After stirring the mixture at 0° C. for 1.5 hour, the reaction mixture is poured into phosphate buffer (pH 7.0, one liter). The precipitated crystal is separated by filtration and dissolved in a mixture of chloroform (2 liters) and tetrahydrofuran (1 liter), and the solution is washed with water, dried and concentrated to dryness under reduced pressure. The residue is crystallized from diethyl ether to give (1R, 5S, 6S)-2-[(4R)-N-methyl- pyrrolidine-2-thion-4-ylthio]-6-[(1R)-1-hydroxyethyl]-1-methylcarbapen -2-em-3-carboxylic acid 4-nitrobenzyl ester (23.5 g) as colorless needles.

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