Synthesis of Repaglinide Congeners

<div><p></p><p>This report describes a synthesis of two potent impurities of repaglinide, benzyl repaglinide <b>1</b> and repaglinide isomer <b>2</b>, from commercially available raw materials: 2-fluoro benzonitrile, (<i>S</i>)-3-methyl-1-[2-(piperidin-1-yl)phenyl]butylamine (<b>5</b>), and 3-ethoxy-[4-(ethoxycarbonyl)phenyl]acetic acid (<b>7</b>). These impurities are the crucial components in determining the quality of the drug substance, repaglinide, during its manufacturing.</p></div>