Diisopropylethylamine → HCID 131725315, compound

Participants

Reaction Steps

To a solution of 3-acetylthio-1-{4-[(1S)-1-(t-butyidimethylsilyloxymethyl)-propylcarbamoyl]-1,3-thiazol-2-yl}azetidine (610 mg, 1.37 mmol) (obtained as described in Reference Example 34) in dimethylformamide (30 ml) was added hydrazine acetate (152 mg, 1.65 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 (814 mg, 1.37 mmol) in acetonitrile (40 ml) was added dropwise to the resulting mixture in an ice bath under an atmosphere of nitrogen, followed by the addition of diisopropylethylamine (955 μl, 5.48 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 10% aqueous sodium chloride 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 (1:2) and ethyl acetate as the eluant to afford p-nitrobenzyl (1R,5S,6S)-2-(1-{4-[(1S)-1-(t-butyidimethylsilyloxymethyl)-propylcarbamoyl]-1,3-thiazol-2-yl}azetidin-3-yl)thio-6-[(R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylate (928 mg, yield 89%) as a pale yellow solid.

Provenance & Evidence