METHOD OF PREPARING ATOMOXETINE AND (R)-NISOXETINE

摘要

PURPOSE: A method for preparing atomoxetine and (R)-nisoxetine is provided to efficiently prepare atomoxetine and (R)-nisoxetine with high optical activity through asymmetric hydrogenation transfer reaction. CONSTITUTION: A method for preparing atomoxetine and (R)-nisoxetine comprises the steps of: preparing a compound of the chemical formula 4 by reducing a compound of the chemical formula 3 through asymmetric transfer hydrogenation in the presence of a catalyst and hydrogen donor; preparing a compound of the chemical formula 5 by reacting the compound of the chemical formula 4 with a nitrile compound; preparing a compound of the chemical formula 6 by reducing the compound of the chemical formula 5 in the presence of BH3; preparing a compound of the chemical formula 7 by introducing a t-butoxycarbonyl group as a blocking group to an amine group of the compound of the chemical formula 6; prep aring a compound of the chemical formula 8 from the compound of the chemical formula 7 using Mitsunobu reaction; preparing a compound of the chemical formula 9 by introducing a methyl group to the compound of the chemical formula 8 in the presence of a base; and deprotecting the compound of the chemical formula 9 in the presence of an acid.