Simple Practical Preparations of Sufentanil from Cheap and Commercially Available 1-methyl-4-piperidon
Abstract:
Novel simple approach was elaborated for the preparation of fentanyl and sufentanil starting from commercially available, cheap 1-methyl-4-piperidone. Compared to existing syntheses new route is shorter, easily scalable, and does not require the use of expensive palladium catalysts, highpressure equipment, and chromatographic separations. Moreover, it allows for to avoidance of working with the unstable norsufentanil, which is prone to a facile acyl migration to the nitrogen atom of the piperidine core even at ambient temperature, resulting in contamination of the target product.
conclusion:
In this study, we developed new practical preparation of sufentanil starting from cheap commercially available 1-methyl-4-piperidone. The entire sequence of transformations is shorter than those reported earlier, all stages proceed in high yields and are easily scalable. The isolation of all intermediates and target product does not require chromatographic purifications. Unlike the majority of previous protocols, this approach does not require the use of the expensive palladium catalysts or their combinations and high pressure equipment for the catalytic debenzylation.
