Process for the preparation of...

Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...

Reexamination Certificate

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Reexamination Certificate

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06861526

ABSTRACT:
A process for preparing (S,S)-cis-2-benzhydryl-3-benzylaminoquinuclidine. The process includes the steps of contacting a compound containing a mixture of R- and S-isomers and having the formulawith an effective amount of a chiral organic acid in the presence of an organic solvent and an effective amount of an organic carboxylic acid for converting the R-isomer into an acid salt of the S isomer, wherein the organic solvent is capable of solubilizing the compound containing the mixture of R- and S-isomers, while precipitating the acid salt and the organic carboxylic acid is different from the chiral organic acid; neutralizing the acid salt with a base to provide an S-isomer of a chiral ketone of the formula; and reacting the chiral ketone with an organic amine in the presence of a Lewis acid to provide the corresponding imine and reducing the imine.

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Lowe, III, J. A. et al. “The Discovery of (2S, 3S)-cis-2-(Diphenylmethyl)-N-[(2-methoxyphenyl)methyl]-1-azabicyclo[2.2.2]octan-3-amine as a Novel, Nonpeptide Substance P Antagonist.”J. Med. Chem., 1992, 35, pp. 2591-2600.
Warawa, E. J. et al. “Quinuclidine Chemistry.4.1Diuretic Properties of cis-3-Amino-2-benzhydrylquinuclidine.”J. Med. Chem., 1975, 18 (6), pp. 587-593.
Seward, E. M., “Quinuclidine-Based NK-1 Antagonists 1: 3-Benzyloxy-1-Arabicyclo[2.2.2]Octanes”,Bioorganic & Medical Chemistry Letters, vol. 3, No. 6, pp. 1361-1366, 1993.

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