Synthesis of the selective muscarinic agonist (3R)-3-(6-chloropyrazin-2-yl)-1-azabicyclo [2.2.2] octane

Abstract
The synthesis of the functionally selective muscarinic agonist (3R)-3-(6-chloropyrazin-2-yl)-1-azabicyclo[2.2.2]octane is described commencing from readily available 4-piperidone. The key feature of this novel process is the preparation and resolution of a piperidin-4-ylacetic acid, with the advantage that high yields of the pure (S)-enantiomer may be obtained by epimerisation of the unwanted enantiomer for further resolution. The reaction sequence is completed by reduction to a chiral 4-hydroxyethylpiperidine and intramolecular N-alkylation to the bicycle 1.

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