Synthesis of the 3-(3,4,5-Trimethoxyphenyl)-pyrrolidine: A New Conformationally Constrained Mescaline Analogue
Synthetic Communications – June 01, 2007
Source: OpenAlex
Summary
A new mescaline analogue was synthesized with an impressive 46% overall yield through a concise four-step process. Starting from N-Cbz-3-pyrrolidine, the synthesis featured a highly effective Heck arylation using 3,4,5-trimethoxybenzene diazonium tetrafluoroborate. Key steps included the dehydration of an intermediate hemiaminal with trifluoroacetic anhydride and subsequent hydrogenation. This novel compound shows promise for activity against 5-HT2 dopamine receptors, highlighting its potential in organic chemistry and synthetic methods for developing biologically relevant molecules.
Abstract
Abstract The total synthesis of the 3‐(3,4,5-trimethoxyphenyl)-pyrrolidine, a new and conformationally constrained mescaline analogue, was accomplished in a concise and efficient manner. The synthetic route encompassed only 4 steps from the starting N-Cbz-3-pyrrolidine, in 46% overall yield. The route features a highly effective Heck arylation of the non-activated olefin N-Cbz-3-pyrrolidine with the 3,4,5-trimethoxybenzene diazonium tetrafluoroborate. The hemiaminal (lactamol) Heck adduct was converted to the mescaline analogue in a sequence of reactions: (a) dehydration of the intermediate hemiaminal 3 with trifluoroacetic acid anhydride, (b) hydrogenation/hydrogenolysis of the endocyclic enecarbamate 6 with H2-Pd/C, and (c) formation of the rather stable mescaline analogue in the form of a hydrochloride salt. The target molecule constitutes a new mescaline analogue with potential activity towards 5‐HT2 dopamine receptors.