Synthesis of the bronchospasmolytic agent flutropium bromide and of some homologous and configuration isomeric compounds

A technically practicable synthesis of unknown N-beta-fluoroalkyl-substituted benzilic acid nortropine esters, among them (8r)-8-(2-fluoroethyl)-3 alpha-hydroxy-1 alpha H, 5 alpha H-tropanium bromide benzilic acid ester (flutropium bromide, Ba 598 BR), and their configuration isomeric quaternary salts via benzilic acid imidazolide is described. The quaternization which takes place with sufficiently high stereo-selectivity leads to configuration isomers which differ not only in their physico-chemical properties but also in their profile of pharmacological action.