Reaktion #978658

Reaktionsgleichung

diisopropylethylamine

3-acetylthio-1-(4-ethoxycarbonyl-1,3-thiazol-2-yl)azetidine

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-[1-(4-ethoxycarbonyl-1,3-thiazol-2-yl)azetidin-3-yl]thio-6-[(R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylate

Ausbeute 75.0%

Lösungsmittel

dimethylformamide

ethyl acetate

acetonitrile

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigethe completion of the reaction
2. 2
   workup.STIRRINGThe mixture was stirred overnight
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 magnesium sulfate
8. 8
   Filtrationfiltered
9. 9
   Einengenconcentrated under reduced pressure
10. 10
    SonstigeThe residue was purified by chromatography on a silica gel column (eluant: ethyl acetate)

Vorschrift

To a solution of 3-acetylthio-1-(4-ethoxycarbonyl-1,3-thiazol-2-yl)azetidine (468 mg, 1.71 mmol) (obtained as described in Reference Example 1) in dimethylformamide (15 ml) was added hydrazine acetate (171.0 mg, 1.86 mmol) at room temperature under an atmosphere of nitrogen and the mixture was stirred for 1.5 hours. 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 (1.02 g, 1.72 mmol) in acetonitrile (30 ml) was added dropwise to the resulting mixture in an ice bath under an atmosphere of nitrogen, followed by the addition of diisopropylethylamine (1.5 ml, 8.61 mmol). The mixture was stirred overnight 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 magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by chromatography on a silica gel column (eluant: ethyl acetate) to afford p-nitrobenzyl (1R,5S,6S)-2-[1-(4-ethoxycarbonyl-1,3-thiazol-2-yl)azetidin-3-yl]thio-6-[(R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylate as a pale yellow solid (752 mg, yield 75%).

Quelle