Diisopropylethylamine → HCID 131725300, compound

Participants

Reaction Steps

To a solution of (3S)-3-acetylthio-1-(4-carbamoyl-1,3-thiazol-2-yl)pyrrolidine (210 mg, 0.721 mmol) (obtained as described in Reference Example 18) in dimethylformamide (10 ml) was added hydrazine acetate (80 mg, 0.865 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 (429 mg, 0.721 mmol) in acetonitrile (20 ml) was added dropwise to the resulting mixture in an ice bath under an atmosphere of nitrogen, followed by the addition of diisopropylethylamine (0.502 ml, 2.88 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 using methylene chloride—10% methanol and methylene chloride as the eluant to afford p-nitrobenzyl (1R,5S,6S)-2-[(3S)-1-(4-carbamoyl-1,3-thiazol-2-yl)pyrrolidin-3-yl]thio-6-[(R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylate as a pale yellow solid (412 mg, yield 100%).

Provenance & Evidence