Introduction of Amine Protecting Groups

Abstract

l-Isoleucine (13.1 g, 100 mmol) is suspended (and partially dissolved) in distilled water (50 ml) and completely dissolved by the addition of N NaOH (100 ml). p-Toluenesulfonyl chloride (26.7 g, 140 mmol) is added to the vigorously stirred solution followed by N NaOH in small portions to maintain the alkalinity of the mixture at about pH 9. Some heat is evolved during the reaction and external cooling with cold water or ice-water is necessary to keep the temperature of the reaction mixture at about 20 °C. After no more alkali is used up [3] stirring is continued at room temperature one hour longer. Any unreacted acid chloride is removed by filtration and the solution acidified with 5 N HC1 (about 20 ml) to Congo. The mixture is stored in the cold overnight; the crystals are collected on a filter, washed with water, dried in air and finally in vacuo over P₂O₅. The product, 25 g (88%) melts at 135–136 °C; [α] ²¹_D − 12° (c 2, 0.5 N KHCO₃) [4, 5].