Acylation with Acetyl-L-isoleucine [1]

Abstract

An enantiomerically pure sample of l-isoleucine [3] (13.1 g, 100 mmol) is added to ice-cold N NaOH (100 ml) and the stirred solution is cooled in an ice-water bath. Chilled N NaOH (20 ml) is added followed by acetic anhydride (2.04 g = 0.94 ml, 20 mmol). The anhydride soon disappears and a homogeneous solution forms. The reaction of the solution should be distinctly alkaline; if necessary a small volume of N NaOH is added to assure alkalinity. The addition of N NaOH and acetic anhydride (the same amounts) is repeated four more times with testing for alkalinity and adjustment, if necessary, after each addition. Stirring is then continued for 30 min. The solution is acidified to Congo with concentrated hydrochloric acid (about 8.5 ml) and crystallization is allowed to proceed at 0 °C for one hour. The crystals are collected on a filter, washed with ice-cold water (25 ml) and dried in air. The crude material (about 8 g) melts at 148–150 °C. Recrystallization from boiling water (80 ml) raises the m.p. to 149–151 °C; concentration of the mother liquor provides a second crop with similar melting point [4].