Synthesis of N ‐Benzyl o ‐Methoxy Phase I Metabolites for Use as Liquid Chromatography‐Quadrupole Time of Flight Standards

ABSTRACT

A novel synthetic method for three Phase I o ‐desmethyl NBOMe metabolites ( 3a , 13b / c ) was developed. The bromo‐( 3a ) and iodo‐( 13b ) metabolites were synthesized across six steps in respective yields of 23 and 21%, while the chloro‐ analogue ( 13c ) required eight steps and was afforded in a 3% overall yield. Having successfully confirmed the structure of the synthesized metabolites, LC‐QToF analysis of the metabolites was conducted by Forensic Science South Australia (FSSA), confirming that the synthetic standards matched the major peaks observed in the LC‐QToF urine sample screen for each of the respective halogen‐substituted metabolites. This result confirmed that the major observed metabolite in the urine samples was the o ‐desmethyl metabolite and that the synthesized metabolites can utilized as standards for toxicological screening.