(2S,4S)-4-acetylthio-2-[4-(2-hydroxyethyl)-1-piperazinylcarbonyl]-1-(4-nitrobenzyloxycarbonyl)pyrrolidine → (2S,4S)-4-Acetylthio-2-{4-[2-(4-nitrobenzyloxycarbonyl)oxyethyl]-1-piperazinylcarbonyl}-1-(4-nitrobenzyloxycarbonyl)pyrrolidine

Participants

Reaction Steps

A solution of 1.10 g of N-nitrobenzyl chloroformate in 10 ml of methylene chloride was added, whilst ice-cooling, to a solution of 1.63 g of (2S,4S)-4-acetylthio-2-[4-(2-hydroxyethyl)-1-piperazinylcarbonyl]-1-(4-nitrobenzyloxycarbonyl)pyrrolidine and 0.62 g of 4-dimethylaminopyridine in 15 ml of methylene chloride and the resulting mixture was stirred at the same temperature for 2 hours. At the end of this time, the reaction mixture was diluted with 100 ml of ethyl acetate, and the dilute solution was washed, in turn, with 100 ml of an aqueous solution of sodium hydrogencarbonate, with 100 ml of water and with 100 ml of an aqueous solution of sodium chloride. The solvent was removed by distillation under reduced pressure, and the resulting residue was purified by column chromatography through silica gel, using a gradient elution method, with mixtures of ethyl acetate and methanol ranging from 30:1 to 25:1 by volume as the eluent to give 1.86 g of the title compound, as a powder. The infrared absorption spectrum and nuclear magnetic resonance spectrum of the compound thus obtained were identical with those of the compound prepared as described in step 90(b)(ii) above.

Provenance & Evidence