Synthesis of a 13C labeled N-cyclopropylamine tetrahydropyridine derivative

The synthesis of 1-(2-C-13)-cyclopropyl-4-phenyl-1,2,3,6-tetrahydropyridine (8) is reported. Attempts were first made to prepare labeled cyclopropylamine via a cyclopropanation/Curtius rearrangement sequence, but the yields were too modest to be suitable for the synthesis of a labeled compound. The preparation of (8) under bar was achieved via cyclopropanation of the N-formyl tetrahydropyridine derivative (21) under bar using the Grignard reagent of ethyl bromide and Ti(O-iOr)(4) as a catalyst. The synthesis proceeded in high yield (82%). The method has a wide potential for the synthesis of other cyclopropyl ring labeled and substituted cyclopropyl ring labeled tetrahydropyridine dervatives which can be used in Monoamine Oxidase (MAO) and Cyt P-450 enzymes mechanistic studies. Copyright (C) 2002 John Wiley Sons, Ltd.