AN ISOLATED ATOMOXETINE IMPURITY, PROCESSES FOR THE PREPARATION OF ATOMOXETINE IMPURITIES AND THEIR USE AS REFERENCE STANDARDS

摘要

The present invention provides isolated N-methyl-3-(3-methylphenoxy)-3-phenylpropylamine hydrochloride, and preparation thereof as well as of N-methyl-3-(4-methylphenoxy)-3-phenylpropylamine hydrochloride and of N-methyl-3-phenoxy-3-phenylpropylamine hydrochloride. The invention further provides the use of the above compounds as reference markers and/or reference standards during the synthesis of Atomoxetine. Also provided is a method of limiting the amounts of the impurities 3FT (3-fluorotoluene), 4FT (4-fluorotoluene), and FB (fluorobenzene) in the 2-fluorotoluene starting material used in the synthesis of Atomoxetine Hydrochloride. The purity of the Atomoxetine Hydrochloride product is ensured by determining the amounts of 3FT, 4FT, and FB in the 2-fluorotoluene starting material with the marker 3-ATM HC1.