Synthesis of sibutramine, a novel cyclobutylalkylamine useful in the treatment of obesity, and its major human metabolites

James E. Jeffery; Frank Kerrigan; Thomas K. Miller; Graham J. Smith; Gerald B. Tometzki

doi:10.1039/P19960002583

Synthesis of sibutramine, a novel cyclobutylalkylamine useful in the treatment of obesity, and its major human metabolites

James E. Jeffery, Frank Kerrigan, Thomas K. Miller, Graham J. Smith and Gerald B. Tometzki

Abstract

Synthetic routes to N-{1-[1-(4-chlorophenyl)cyclobutyl]-3-methylbutyl}-N,N-dimethylamine (sibutramine) 1 and its demethylated and hydroxylated human metabolites N-{1-[1-(4-chlorophenyl)cyclobutyl]-3-methylbutyl}-N-methylamine 2, 1-[1-(4-chlorophenyl)cyclobutyl]-3-methylbutylamine 3, 4-amino-4-[1-(4-chlorophenyl)cyclobutyl]-2-methylbutan-1-ol 4 and c-3-(1-amino-3-methylbutyl)-3-(4-chlorophenyl)cyclobutan-r-1-ol 5a are described. Key steps are tandem Grignard–reduction reactions on 1-(4-chlorophenyl)cyclobutanecarbonitrile 7 and its 3-(tetrahydropyran-2-yloxy)-substituted analogue 14 and a convenient one-pot conversion of 4-chlorophenylacetonitrile 6 into the 3-hydroxycyclobutanecarbonitrile 13.

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J. Chem. Soc., Perkin Trans. 1, 1996, 2583-2589

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Synthesis of sibutramine, a novel cyclobutylalkylamine useful in the treatment of obesity, and its major human metabolites

J. E. Jeffery, F. Kerrigan, T. K. Miller, G. J. Smith and G. B. Tometzki, J. Chem. Soc., Perkin Trans. 1, 1996, 2583

DOI: 10.1039/P19960002583

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Journal of the Chemical Society, Perkin Transactions 1

Synthesis of sibutramine, a novel cyclobutylalkylamine useful in the treatment of obesity, and its major human metabolites

Abstract

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Synthesis of sibutramine, a novel cyclobutylalkylamine useful in the treatment of obesity, and its major human metabolites

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