合成路线1

This compound can be obtained in a simple way: Under nitrogen, borontrifluoride etherate solution is added to heated 2-methyl-1-propanol (II), and 1-chloro-2,3-epoxypropane (I) is added. When the reaction is completed, pyrrolidine (IV) is added to obtain alpha-[2-methyl-propoxymethyl]-1-pyrrolidine-ethanol (V). 1-[2-Chloro-3-(2-methylpropoxy)propyl]pyrrolidine (VI) is obtained by chlorination with thionyl chloride of the subsequent amino alcohol. The condensation of 1-propynyl-1-cyclohexanol (VII) with 1-[2-chloro-3-(2-methylpropoxy)propyl]pyrrolidine (VI) in toluene and sodium hydroxide in water affords dopropidil. Due to the pyrrolidine shift mechanism, the reaction yields the correct structure, confirmed by 1H and 13C NMR as well as by mass spectra and X-ray analysis. The pyrrolidine shift mechanism is explained by the assumption of an intermediate aziridinium ion (VIII), which is opened regiospecifically at the less hindered C-N bond by the nucleophile ion.