Synthesis of (1‐(Aminomethyl)‐2,3‐dihydro‐1H‐inden‐3‐yl)methanol: Structural Confirmation of the Main Band Impurity Found in Varenicline®Starting Material

Autor: Chiara Bezze, Robert A. Singer, Megan McMahon, Mariano Stivanello, Gregory J. Withbroe, Handfield Robert Eugene, Paul E. Concannon, Jason D. McKinley, Timothy J. N. Watson, Lucia Leoni, Busch Frank R
Rok vydání: 2008
Předmět:
Zdroj: Synthetic Communications. 38:441-447
ISSN: 1532-2432
0039-7911
DOI: 10.1080/00397910701771231
Popis: Described here is the synthesis of (1‐(aminomethyl)‐2,3‐dihydro‐1H‐inden‐3‐yl)methanol 1, the previously unidentified impurity found in the synthesis of 2,1 providing a confirmation of the structure. Fabbrica Italiano Sintetici (FIS), working in conjunction with Pfizer Groton, reported an unidentified impurity, referred to as the “main band impurity”, in 2 at levels of 0.4 to 0.8%. The structure was postulated to be 1, the open‐ring product of the lithium aluminum hydride (LAH) reduction of 3 to 2. Although the cis isomer of 1 was previously reported in the literature,2 a much shorter racemic synthesis was developed using intermediates employed for the production of Varenicline®. Several reducing agents were screened for the synthesis of 1, with LiAlH4 followed by basic workup conditions giving optimal results. High performance liquid chromatography (HPLC) analysis ultimately confirmed the structure of 1 as the main band impurity generated during the synthesis of 2.
Databáze: OpenAIRE
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