Reaktion #978666

Reaktionsgleichung

diisopropylethylamine

(3S)-3-acetylthio-1-(4-cyano-1,3-thiazol-2-yl)pyrrolidine

hydrazine acetate

sodium hydrogencarbonate

p-nitrobenzyl (1R,5S,6S)-2-diphenylphosphoryloxy-6-[(R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylate

→

p-nitrobenzyl (1R,5S,6S)-2-[(3S)-1-(4-cyano-1,3-thiazol-2-yl)pyrrolidin-3-yl]thio-6-[(R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylate

Ausbeute 84.0%

Lösungsmittel

dimethylformamide

ethyl acetate

acetonitrile

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigethe completion of the reaction
2. 2
   workup.STIRRINGThe mixture was stirred for 2 hours
3. 3
   workup.ADDITIONwere added to the reaction mixture
4. 4
   workup.STIRRINGThe resulting mixture was shaken in a separatory funnel
5. 5
   Sonstigethe ethyl acetate layer was separated
6. 6
   Waschenwashed with 0.5 M hydrochloric acid, saturated aqueous sodium hydrogencarbonate solution and saturated aqueous sodium chloride solution
7. 7
   Trocknendried over anhydrous sodium sulfate
8. 8
   Filtrationfiltered
9. 9
   Einengenconcentrated under reduced pressure
10. 10
    SonstigeThe residue was purified by chromatography on a silica gel column

Vorschrift

To a solution of (3S)-3-acetylthio-1-(4-cyano-1,3-thiazol-2-yl)pyrrolidine (137 mg, 0.541 mmol) (obtained as described in Reference Example 19) in dimethylformamide (7 ml) was added hydrazine acetate (60 mg, 0.649 mmol) at room temperature under an atmosphere of nitrogen and the mixture was stirred for 1 hour. After checking the completion of the reaction, a solution of p-nitrobenzyl (1R,5S,6S)-2-diphenylphosphoryloxy-6-[(R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylate (322 mg, 0.541 mmol) in acetonitrile (16 ml) was added dropwise to the resulting mixture in an ice bath under an atmosphere of nitrogen, followed by the addition of diisopropylethylamine (0.376 ml, 2.16 mmol). The mixture was stirred for 2 hours while gradually raising the temperature to room temperature. After checking the completion of the reaction, ethyl acetate and saturated aqueous sodium hydrogencarbonate solution were added to the reaction mixture. The resulting mixture was shaken in a separatory funnel and the ethyl acetate layer was separated, washed with 0.5 M hydrochloric acid, saturated aqueous sodium hydrogencarbonate solution and saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by chromatography on a silica gel column using n-hexane: ethyl acetate (1:3) and ethyl acetate as the eluant to afford p-nitrobenzyl (1R,5S,6S)-2-[(3S)-1-(4-cyano-1,3-thiazol-2-yl)pyrrolidin-3-yl]thio-6-[(R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylate as a pale yellow solid (251 mg, yield 84%).

Quelle