反应详情

To a solution of (2S,4S)-4-acetylthio-1-p-nitrobenzyloxycarbonyl-2-(4-sulfamoylphenyl)thiomethylpyrrolidine (1.48 g, 2.82 mmol) in a mixture of methanol (30 ml) with chloroform (30 ml), 1N aqueous NaOH (3.11 ml, 3.11 mmol) was added in a nitrogen stream at 5° C., and the resulting reaction solution was stirred at the same temperature for 1 hour. The reaction solution was neutralized with 1N aqueous HCl (3.11 ml, 3.11 mmol), and the solvent was distilled off in vacuo. To a solution of the residue and p-nitrobenzyl (1R,5S,6S)-2-diphenylphosphoryloxy-6-[(1R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylate (2.24 g, 3.78 mmol) in acetonitrile (50 ml), DIPA (0.78 ml, 4.48 mmol) was added, and the reaction solution was stirred at 5° C. overnight. To the reaction solution, ethyl acetate was added. The solution was washed successively with water, 10% aqueous citric acid, saturated aqueous sodium hydrogencarbonate and saturated aqueous sodium chloride. Then, it was dried over anhydrous sodium sulfate, and the solvent was distilled off in vacuo. The resulting residue was purified by silica gel column chromatography (heptane-ethyl acetate) to give p-nitrobenzyl (1R,5S,6S)-6-[(1R)-1-hydroxyethyl]-1-methyl-2-[(3S,5S)-1-p-nitrobenzyloxycarbonyl-5-(4-sulfamoylphenylthiomethyl)pyrrolidin-3-ylthio)-1-carbapen-2-em-3-carboxylate (1.57 g, yield: 67%).

1. additionwas added in a nitrogen stream at 5° C.
2. customthe resulting reaction solution
3. distillationthe solvent was distilled off in vacuo
4. stirringthe reaction solution was stirred at 5° C. overnight
5. washThe solution was washed successively with water, 10% aqueous citric acid, saturated aqueous sodium hydrogencarbonate and saturated aqueous sodium chloride
6. dry with materialThen, it was dried over anhydrous sodium sulfate
7. distillationthe solvent was distilled off in vacuo
8. customThe resulting residue was purified by silica gel column chromatography (heptane-ethyl acetate)