Reaction of N,N-Dimethyltryptamine with Dichloromethane Under Common Experimental Conditions

[Image: see text] A large number of clinically used drugs and experimental pharmaceuticals possess the N,N-dimethyltryptamine (DMT) structural core. Previous reports have described the reaction of this motif with dichloromethane (DCM), a common laboratory solvent used during extraction and purification, leading to the formation of an undesired quaternary ammonium salt byproduct. However, the kinetics of this reaction under various conditions have not been thoroughly described. Here, we report a series of experiments designed to simulate the exposure of DMT to DCM that would take place during extraction from plant material, biphasic aqueous work-up, or column chromatography purification. We find that the quaternary ammonium salt byproduct forms at an exceedingly slow rate, only accumulates to a significant extent upon prolonged exposure of DMT to DCM, and is readily extracted into water. Our results suggest that DMT can be exposed to DCM under conditions where contact times are limited (<30 min) with minimal risk of degradation and that this byproduct is not observed following aqueous extraction. However, alternative solvents should be considered when the experimental conditions require longer contact times. Our work has important implications for preparing a wide-range of pharmaceuticals bearing the DMT structural motif in high yields and purities.