Diisopropylethylamine → HCID 131725338, compound

Participants

Reaction Steps

To a solution of 3-acetylthio-1-{4-[1-(p-nitrobenzyloxycarbonyl)-azetidin-3-ylcarbamoyl]-1,3-thiazol-2-yl}azetidine (400 mg, 0.814 mmol) (obtained as described in Reference Example 54) in dimethylformamide (20 ml) was added hydrazine acetate (90 mg, 0.977 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 (484 mg, 0.814 mmol) in acetonitrile (25 ml) was added dropwise into the resulting mixture in an ice bath under an atmosphere of nitrogen, followed by the addition of diisopropylethylamine (568 μl, 3.26 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 sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by chromatography on a silica gel column (eluant: ethyl acetate→ethyl acetate:methanol (9:1)) to afford p-nitrobenzyl (1R,5S,6S)-2-(1-{4-[1-(p-nitrobenzyloxycarbonyl)-azetidin-3-ylcarbamoyl]-1,3-thiazol-2-yl}azetidin-3-yl)thio-6-[(R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylate (496 mg, yield 77%) as a pale yellow solid.

Provenance & Evidence