A Practical, Kilogram-Scale Implementation of the Wolff−Kishner Reduction

A safe and practical strategy has been developed for the large-scale preparation of imidazole 7. The key transformation involved the Wolff-Kishner reduction of the sterically demanding neopentyl-trifluoromethylcyclopropyl imidazole ketone 8. The described process provided the desired product in 74% overall yield without recourse to chromatographic purification. Safety considerations which allowed for the reaction to be conducted safely on kilogram scale are discussed.