Teva Pharmaceutical Fine Chemicals S.r.l.

Paolo Riva

Eugenio Castelli

Stefano Bianchi

Paola Daverio

Silvia Mantovani

Alessandra Vailati

Giuseppe Lo Monaco

Stable Atomoxetine hydrochloride, a process for the manufacture thereof, the use of stable Atomoxetine Hydrochloride for making a pharmaceutical formulation, a process for the preparation of any form of Atomoxetine Hydrochloride, and an analytical method for analyzing the stability of Atomoxetine Hydrochloride are provided.

Stable atomoxetine hydrochloride, a process for the preparation thereof, and an analytical control of its stability

The present invention provides improved processes for the preparation of atomoxetine hydrochloride under reaction conditions that improve reaction yields and facilitate commercial synthesis. In particular, the invention is directed to the synthesis of atomoxetine HCl by adding HCl to a mixture of (R)-(&#x2212;)-tomoxetine (S)-(+)-mandelate with an organic solvent, with or without a base and water.

Process for the preparation of atomoxetine hydrochloride

Provided are processes for preparing tomoxetine comprising reacting N-methyl-3-hydroxy-3-phenylpropylamine with dimethylsulfoxide (DMSO) and 2-fluorotoluene in the presence of an alkali base to form tomoxetine. Also provided is the conversion of said tomoxetine into atomoxetine or a pharmaceutically acceptable salt thereof.

Processes for the preparation of tomoxetine

The present invention provides a process for the optical resolution of racemic tomoxetine under reaction conditions that improve reaction yields and optical purity. The invention also provides an epimerization process for the (S)-(+) enantiomer. The invention further provides the conversion of the enantiomer obtained from the optical resolution into atomoxetine or a pharmaceutically acceptable salt thereof.

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Monza, Italy

Paolo Riva