Kinetically-controlled displacement by azide on an allylic chloride: Synthesis of a highly potent serotonin-3 receptor ligand prototype

Article abstract of DOI:10.1016/S0040-4020(01)80973-X

The discovery and selective synthesis of a novel and highly potent serotonin-3 receptor ligand, 4-amino-5-chloro-2-methoxy-N-(1-azabicyclo[2.2.2]-oct-2-enyl-2-methyl) benzamide (4) are described. The key step in the preparation of 4 involves an unusual example of a kinetically controlled displacement to provide a thermodynamically disfavored allylic azide isomer. This azide is a precursor to 2-aminomethyl-1-azabicyclo[2.2.2]oct-2-ene, a convergent intermediate for the synthesis of analogs related to 4.