SYNTHESIS OF THE SELECTIVE MUSCARINIC AGONIST 3-(6-CHLOROPYRAZIN-2-YL)-1-AZABICYCLO[2.2.2]OCTANE

The synthesis of the functionally selective muscarinic agonist -(6-chl oropyrazin-2-yl)-1-azabicyclo-[2.2.2]octane is described commencing fr om readily available 4-piperidone. The key feature of this novel proce ss is the preparation and resolution of a piperidin-4-ylacetic acid, w ith the advantage that high yields of the pure (S)-enantiomer may be o btained by epimerisation of the unwanted enantiomer for further resolu tion. The reaction sequence is completed by reduction to a chiral 4-hy droxyethylpiperidine and intramolecular N-alkylation to the bicycle 1.