To a solution of (2S,4S)-4-acetylthio-1-(4-nitrobenzyloxycarbonyl)-2-(3-carboxyphenylcarbamoyl)pyrrolidine (0.49 g, 1 mM) in dichloromethane (10 ml) was added oxalyl chloride (0.20 ml. 1.1 mM) and dimethylformamide (2-3 drops). After 1 hour a further amount of oxalyl chloride (0.20 ml, 1.1 mM) and DMF (2-3 drops) were added and the mixture stirred for a further hour. The solution was evaporated to leave a yellow gum. The gum was dissolved in dichloromethane (10 ml) and added to a suspension of 4-nitrobenzyl 2-aminoethanoate hydrochloride salt (0.30 g, 1.2 mM) and N-methylmorpholine (0.27 ml, 2.4 mM) in dichloromethane (10 ml). After 17 hours the mixture was diluted with dichloromethane (80 ml), washed with water (20 ml), brine (20 ml) and dried (MgSO4). Purification by flash chromatography through silica using a gradient of dichloromethane to ethyl acetate as eluent gave (2S,4S)-4-acetylthio-1-(4-nitrobenzyloxycarbonyl)-2-(3-(4-nitrobenzyloxycarbonylmethylaminocarbonyl)phenylcarbamoyl)-pyrrolidine (380 mg).
