This reactivity was therefore exploited to negate the need for pivaloate ester cleavage and hydroxy activation. Following formation of 6 from 5, the direct displacement of pivaloate was promoted simply by increasing the reaction temperature from 90 °C to 110 °C, to give a smooth one-pot conversion into berberine in 82 % yield. Pure berberine chloride was obtained by adding NaOH to convert the isoquinolinium salt into its hydroxide adduct which was extracted with CH2Cl2.1 Subsequent treatment with HCl regenerated the chloride salt.