Challenges in the automated synthesis of [ 18 F]-1-fluoroethyl tryptophan: Formation of both O- and N-alkylated products

• Published in: Applied radiation and isotopes Vol. 131; pp. 41 - 48
• Main Authors: Venkatachalam, T K, Stimson, D H R, Pierens, G K, Bhalla, R, Reutens, D C
• Format: Journal Article
• Language: English
• Published: England 01-01-2018
• ISSN: 0969-8043; 1872-9800
• DOI: 10.1016/j.apradiso.2017.10.047

[
F]Fluoroethyl tosylate was synthesized using an automated "Synthra" module using ethylene di-tosylate and [
F]fluoride/K
/K
CO
in acetonitrile. [
F]Fluoroethyl tosylate was purified by semi-preparative HPLC followed by reformulation using a C18 Sep-Pak cartridge and eluted with DMF. Using this [
F]fluoroethyl tosylate, we attempted to alkylate protected tryptophan aiming to obtain the N-[
F]fluoroethyl-t-Boc-tryptophan methyl ester. Initial attempts resulted in the formation of the O-alkylated, rather than N-alkylated product. Manual removal of the cartridge from the automated module, followed by an extended drying of the cartridge under high flow nitrogen, was required to form the desired N-alkylated product. This demonstrates that the drying process in automated modules requires modification for sensitive N-alkylation of compounds and may be essential for compounds like tryptophan methyl ester that have multiple potential sites of alkylation in their chemical structure.