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

Participants

Reaction Steps

105 g of (2S,4R)-4-hydroxy-2-{4-[2-(4-nitrobenzyloxycarbonyl)oxyethyl]-1-piperazinylcarbonyl}-1-(4-nitrobenzyloxycarbonyl)pyrrolidine (prepared as described in Preparation 15) and 55 g of triphenylphosphine were dissolved in 700 ml of tetrahydrofuran, and a solution of 36.5 g of diethyl azodicarboxylate in 100 ml of tetrahydrofuran was added dropwise to it, whilst ice-cooling. The resulting mixture was then stirred at the same temperature for 10 minutes. At the end of this time, a solution of 15.9 g of mercaptoacetic acid in 100 ml of tetrahydrofuran was added dropwise to the mixture, and the resulting mixture was stirred at room temperature for 1 hour. The mixture was then concentrated by evaporation under reduced pressure. The concentrate was dissolved in 1.5 liters of ethyl acetate and washed with water and with an aqueous solution of sodium chloride, in that order. The organic layer was dried over anhydrous sodium sulfate and then concentrated by evaporation under reduced pressure. The resulting residue was mixed with 400 ml of diisopropyl ether and a soluble material was removed. This procedure was repeated four times in all. The residue was subjected to column chromatography through 3 kg of silica gel using mixtures of ethyl acetate and methanol ranging from 1:0 to 20:1 by volume as the eluent. Those fractions containing the title compound were collected and concentrated by evaporation under reduced pressure, to afford 88.4 g of the title compound as a colorless powder.

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