Réaction #5154

Équation de réaction

diisopropylethylamine

salt

(2S, 4S)-2-carbamoyl-4-mercapto-1,1-dimethylpyrrolidinium

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

diisopropylethylamine

diphenylphosphoryl chloride

→

title compound

(1R, 5S, 6S)-2-[(2S, 4S)-2-Carbamoyl-1,1-dimethylpyrrol idinium-4-ylthio]-6-[(1R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylate

Solvants

tetrahydrofuran

phosphate

palladium-on-charcoal

acetonitrile

acetonitrile

Conditions de réaction

Traitement

1. 1
   Températurecooling
2. 2
   workup.STIRRINGthe mixture was then stirred for 7 hours
3. 3
   workup.WAITto stand for 2 days at the same temperature
4. 4
   workup.DISTILLATIONThe solvent was then distilled off under reduced pressure
5. 5
   Lavagethe residue was washed repeatedly by decantation
6. 6
   Autredried under reduced pressure
7. 7
   Autreto afford a crude product
8. 8
   AutreAt the end of this time, an insoluble material was removed by filtration with the help of a Celite (trade mark)
9. 9
   Filtrationfilter aid
10. 10
    Lavagethe filtrate was washed with diethyl ether
11. 11
    ConcentrationThe aqueous layer was then concentrated by evaporation under reduced pressure
12. 12
    Lavage(Mitsubishi Chemical Industries, Ltd.) and the fractions eluted with a 5% by volume aqueous acetone solution
13. 13
    Concentrationwere concentrated by evaporation under reduced pressure
14. 14
    Autreto afford a crude product as a yellow powder
15. 15
    AutreThis crude product was purified by chromatography
16. 16
    LavageThe fractions eluted with 5% and 10% by volume aqueous methanolic solutions
17. 17
    Autrewere collected
18. 18
    Concentrationconcentrated by evaporation under reduced pressure

Mode opératoire

0.20 ml of diisopropylethylamine and 0.24 ml of diphenylphosphoryl chloride were added dropwise, whilst ice-cooling, to a solution of 400 mg of 4-nitrobenzyl (1R, 5R, 6S)-6-[(1R)-1-hydroxyethyl]-1-methyl-2-oxo-1-carbapenam-3-carboxylate in 4 ml of dry acetonitrile, and the mixture was stirred at the same temperature for 1 hour. At the end of this time, 0.46 ml of diisopropylethylamine and a solution of the salt prepared in step (1) above in 3 ml of acetonitrile were added to the reaction mixture, whilst ice-cooling, and the mixture was then stirred for 7 hours and then allowed to stand for 2 days at the same temperature. The solvent was then distilled off under reduced pressure, and the residue was washed repeatedly by decantation using diethyl ether and dried under reduced pressure to afford a crude product. This crude product was then dissolved in a mixture of 30 ml of tetrahydrofuran and 30 ml of a 0.1M phosphate buffer (pH 7.0) and hydrogenated at room temperature for 2.5 hours in the presence of 555 mg of 10% w/w palladium-on-charcoal. At the end of this time, an insoluble material was removed by filtration with the help of a Celite (trade mark) filter aid, and the filtrate was washed with diethyl ether. The aqueous layer was then concentrated by evaporation under reduced pressure. The residue was adsorbed on a column of Diaion (trade mark) HP-20AG (Mitsubishi Chemical Industries, Ltd.) and the fractions eluted with a 5% by volume aqueous acetone solution were concentrated by evaporation under reduced pressure, and the residue was lyophilized to afford a crude product as a yellow powder. This crude product was purified by chromatography using a Lobar column (Merck Co., LiChroprep RP-8, size B). The fractions eluted with 5% and 10% by volume aqueous methanolic solutions were collected and concentrated by evaporation under reduced pressure, and the residue was lyophilized to afford 100 mg of the title compound.

Source