The Use of Glycidyl Ethers Involving Aziridinium Intermediates and Other Methodology for the Preparation of Enantiomerically Pure Drug Candidates

An enantiospecific 1,2-amine migration process through an aziridinium intermediate involving ring-opening with potassium phthalimide derivatives to produce precursors to drug candidates was developed. The precursor amine derivatives were readily available by epoxide opening of simple glycidyl ether derivatives. The regioselectivity of the process was shown to provide approximately 85% of the desired rearranged product with subsequent conversion to the desired drug candidate occurring with excellent purity. An alternative approach using the same glycidyl ether derivatives as starting materials that overcame this regiochemical limitation was subsequently demonstrated.