Preparation of Active Esters

Abstract

A mixture of triethylamine (15.2 g = 21.0 ml, 150 mmol) and chloroacetonitrile (15.1 g = 12.6 ml, 200 mmol) is cooled in an ice-water bath while N-benzyloxycarbonyl-S-benzyl-l-cysteine [3] (34.5 g, 100 mmol) is added, in small portions, with stirring. The addition of the protected amino acid requires about 15 minutes. Stirring and cooling are continued for about 30 min and the mixture is stored at room temperature overnight. The thick mass is diluted with ethyl acetate (200 ml), the insoluble material (triethylammonium chloride) is removed by filtration and washed with ethyl acetate (50 ml). The solution is extracted with 0.5 N HCl (100 ml), 0.5 N KHCO₃ (100 ml) [4] and water (100 ml), dried over anhydrous Na₂SO₄ and evaporated to dryness in vacuo. The residue is crystallized from ether-hexane. The activated ester (31.2 g, 81%) melts at 65–67 °C; [α] ¹⁹_D −23° (c 4, CHCl₃); −45° (c 4, AcOH). Recrystallization from ether-hexane can raise the melting point to 67–68 °C.