PT - JOURNAL ARTICLE AU - Tanpreet Kaur AU - Allen Brooks AU - Peter Scott TI - Optimization of the Production of 2,2,2-[<sup>18</sup>F]trifluoroethyl Tosylate for use as a Prosthetic Group DP - 2021 May 01 TA - Journal of Nuclear Medicine PG - 1453--1453 VI - 62 IP - supplement 1 4099 - http://jnm.snmjournals.org/content/62/supplement_1/1453.short 4100 - http://jnm.snmjournals.org/content/62/supplement_1/1453.full SO - J Nucl Med2021 May 01; 62 AB - 1453Objectives: The preparation of 2,2,2-[18F]trifluoroethyl tosylate has been previously described from it gem-difluoro precursor as well as a preliminary look at its utility as a prosthetic group for the preparation of more complicated PET imaging agents.[1] The recent adaption of the chemistry to produce [18F]N-methyl lansoprazole using the preformed enol ether of the gem-difluoro in high molar activity at two sites as part of a clinical study has created renewed interest in further developing the chemistry for preparation of aliphatic radiofluorinated trifluoromethyl groups.[2] In the clinical study each site used a slightly different method for providing the proton source to complete the addition of HF across the gem-difluoro enol ether, one site using the 2-propanol previously described and the other a saturated solution of ammoium chloride (NH4Cl). In this work, the optimization of the preparation of 2,2,2-[18F]trifluoroethyl tosylate for use as a prosthetic group is explored. Methods: Fluorine-18 was prepared by standard techniques as K[18F]F-kryptofix. 1,1-Difluorovin-2-yl 4-toluenesulfonate precursor (5.0 mg) in DMSO (500 μL) was treated with either 2-propanol or saturated aqueous NH4Cl solution. The percent yield of the desired product and the ratio of the radiolabelled [18F]trifluormethyl to [18F]difluorovinyl side product were compared. The labelling precursor was dissolved in DMSO in the presence of either isopropanol or sat. NH4Cl. Attempts to accomplish a one pot synthesis with the prosthetic group were next undertaken. The alkylation of an amine with the [18F]trifluoroethyl tosylate with and without base using various solvents and temperatures was explored. Results: Both procedures, 2-propanol and NH4Cl solution, resulted in the formation of desired product with 2-propanol providing a higher yield. In prior work with the prosthetic group, it was not stipulated if the process was one-pot or if the prosthetic group required purification prior to use in the alkylation reaction. In our evaluation, the alkylation was only accomplished in a modest yield, with the best conditions being the pretreatment of the amine with sodium hydride (RCY 0.4%). It is likely that isolation of pure intermediate is required for efficient alkylation. Results are summarized in Figure 1. Conclusions: Both 2-propanol and NH4Cl solution can be utilized to prepare [18F]trifluoroethyl tosylate, with 2-propanol providing slightly better conversion. Our evaluation shows that the prosthetic group requires purification for efficient alkylation to install [18F]trifluoroethyl groups on drug like scaffolds. Further optimization is in progress and will be disclosed in the future. References: [1] P. J. Riss, V. Ferrari, L. Brichard, P. Burke, R. Smith, Franklin I. Aigbirhio, Org. Biomol. Chem., 2012,10, 6980-6986. [2] A. F. Brooks, A. J. Mufarreh, X. Shao, T. Kaur, J. Stauff, J. Arteaga, M. R. Kilbourn, Peter J. H. S, ACS Med. Chem. Lett. 2020, 11, 2300-2304.