反应详情

温度

35 °C

A suspension of 1.8 g of (2S,4S)-2-carboxy-4-(4-methoxybenzylthio)-1-methylpyrrolidine [prepared as described in step (ii) above] and 1.26 g of N,N'-carbonyldiimidazole in 18 ml of dry acetonitrile was stirred at 35° C. for 25 minutes. A solution of 3.7 g of 1-(4-nitrobenzyloxycarbonyl)homopiperazine trifluoroacetate in 20 ml of dry acetonitrile and 2.0 ml of N,N-diisopropylethylamine were then simultaneously added dropwise, whilst ice-cooling, to the reaction mixture, and the resulting mixture was stirred at room temperature for 8 hours, after which it was allowed to stand overnight at room temperature. At the end of this time, the reaction mixture was concentrated by evaporation under reduced pressure, and the residue was dissolved in ethyl acetate. The solution was washed with an aqueous solution of sodium hydrogencarbonate, with a phosphate buffer solution (pH 6.86), with water and with an aqueous solution of sodium chloride, in that order. The ethyl acetate layer was then dried over anhydrous magnesium sulfate, and the solvent was removed by distillation under reduced pressure. The resulting residue was purified by column chromatography through silica gel (Merck Art 9385), using a 95:5 by volume mixture of acetonitrile and water, to give 2.5 g of the title compound.

1. temperaturecooling, to the reaction mixture
2. stirringthe resulting mixture was stirred at room temperature for 8 hours
3. waitto stand overnight at room temperature
4. concentrationAt the end of this time, the reaction mixture was concentrated by evaporation under reduced pressure
5. dissolutionthe residue was dissolved in ethyl acetate
6. washThe solution was washed with an aqueous solution of sodium hydrogencarbonate, with a phosphate buffer solution (pH 6.86), with water and with an aqueous solution of sodium chloride, in that order
7. dry with materialThe ethyl acetate layer was then dried over anhydrous magnesium sulfate
8. customthe solvent was removed by distillation under reduced pressure
9. customThe resulting residue was purified by column chromatography through silica gel (Merck Art 9385)
10. additionby volume mixture of acetonitrile and water