Synthesis of Acyl Derivatives of Cotarnine

Abstract

A. Cotarnine (1). A 250-mL, round-bottomed, three-necked flask is equipped with a magnetic stir bar (elliptical, 32 x 16 mm, Teflon-coated). The flask is dried under vacuum (1.8 mmHg) with a propane torch and then allowed to cool to 25 °C. The dried flask is then charged with nitric acid (150 mL, 18% (v/v) in H2O) and fitted with a reflux condenser complete with a nitrogen inlet, a thermometer, and the final neck is sealed with a rubber septum (Figure 1) (Notes 2, and 3). Slow stirring of the solution (150 rpm) is commenced. The rubber septum is briefly removed, the solid (S,R)-Noscapine (20 g, 48.4 mmol, 1.0 equiv) is added to the flask in a single portion at 25 °C, after which the rubber septum is replaced (Notes 4 and 5). The mixture is observed to turn from a white to slightly yellow turbid solution.