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Identification, Synthesis, and Characterization of Potential Dichloro Impurity: N,N-Dimethyl-3-Phenyl-2, 3-Dichloropropylamine in the Synthesis of Atomoxetine

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An unknown impurity was identified using the HPLC technique at relative retention time ~1.07 with a peak area of 0.45% during the commercial synthesis of atomoxetine. The profile of the new impurity was established using 1H NMR and LCMS spectroscopy and found to be N,N-dimethyl-3-phenyl-2,3-dichloropropylamine. Adetailed analysis was made using different experimental techniques to find the cause of dichloro impurity. It has been recognized that thionyl chloride (SOCl2) was the potential cause of the formation of the dichloro impurity. The mechanism of the formation of the impurity using retrosynthetic analysis and synthetic strategy was also discussed. The synthesized impurity was compared with the formed impurity by employing LCMS, IR, and NMR spectroscopy. Astrategy for minimizing this potential dichloro impurity was discussed.

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Authors and Affiliations

  1. Department of Analytical Chemistry, Aurobindo Pharma Ltd, Pydibhimavaram, India

    Sateesh Kumar Pinninti & Sivaganesh Tene

  2. Department of Inorganic & Analytical Chemistry, Andhra University, Visakhapatnam, 530003, Andhra Pradesh, India

    Siva Rao T

  3. Department of Organic Chemistry, Gayatri Vidya Parishad College for Degree and PG Courses (A), Rushikonda, Visakhapatnam, 530045, India

    Karteek Rao Amperayani & Uma Devi Parimi

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  1. Sateesh Kumar Pinninti
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  2. Sivaganesh Tene
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  3. Siva Rao T
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  4. Karteek Rao Amperayani
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  5. Uma Devi Parimi
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Correspondence to Karteek Rao Amperayani.

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Pinninti, S.K., Tene, S., T, S.R. et al. Identification, Synthesis, and Characterization of Potential Dichloro Impurity: N,N-Dimethyl-3-Phenyl-2, 3-Dichloropropylamine in the Synthesis of Atomoxetine. Pharm Chem J 57, 1304–1313 (2023). https://doi.org/10.1007/s11094-024-03039-8

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  • DOI: https://doi.org/10.1007/s11094-024-03039-8

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