Diisopropylethylamine → p-nitrobenzyl (1R,5S,6S)-2-{1-[4-(3-methoxyazetidine-1-carbonyl)-1,3-oxazol-2-yl]azetidin-3-yl}thio-6-[(R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylate

Participants

Reaction Steps

To a solution of 3-acetylthio-1-(4-(3-methoxyazetidine-I-carbonyl)-1,3-oxazol-2-yl)azetidine (330 mg, 1.06 mmol) (obtained as described in Reference Example 73) in dimethylformamide (17 ml) was added hydrazine acetate (117 mg, 1.27 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 (630 mg, 1.06 mmol) in acetonitrile (32 ml) was added dropwise into the resulting mixture in an ice bath under an atmosphere of nitrogen, followed by the addition of diisopropylethylamine (739 μl, 4.24 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% 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 (eluant: ethyl acetate:methanol (95:5→9:1)) to afford p-nitrobenzyl (1R,5S,6S)-2-{1-[4-(3-methoxyazetidine-1-carbonyl)-1,3-oxazol-2-yl]azetidin-3-yl}thio-6-[(R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylate (550 mg, yield 85%) as a pale yellow solid.

Provenance & Evidence