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The 18 F‐labelled alkylating agent 2,2,2‐trifluoroethyl triflate: Synthesis and specific activity
Author(s) -
Johnström Peter,
StoneElander Sharon
Publication year - 1995
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.2580360605
Subject(s) - chemistry , trifluoromethanesulfonate , nucleophile , toluene , medicinal chemistry , alkylation , fluoride , catalysis , organic chemistry , inorganic chemistry
Abstract A method for synthesizing the alkylating agent 2,2,2‐trifluoroethyl triflate labelled with [ 18 F]fluoride in the two position is presented. Ethyl [2‐ 18 F]‐trifluoroacetate was synthesized by the nucleophilic reaction of [ 18 F]F − with ethyl bromodifluoroacetate in DMSO (45‐60%, 5 min, 80 °C) and subsequently converted to [2‐ 18 F]‐2,2,2‐trifluoroethanol using alane in THF (85‐95%, 2 min, 40 °C). Reaction with triflic anhydride in 2,6‐lutidine produced [2‐ 18 F]‐2,2,2‐trifluoroethyl triflate (70‐80%, 1 min, 0 °C). In all three cases the product was removed from the reaction vessel by heating to distil under a stream of nitrogen. [2‐ 18 F]‐2,2,2‐Trifluoroethyl triflate was used to label 2‐oxoquazepam by N ‐alkylation in a toluene: DMF mixture (80‐85%, 20 min, 120 °C). Although no‐carrier‐added [ 18 F]F − was used, considerable unlabelled ethyl trifluoroacetate was produced in the first reaction. Varying the conditions for the fluoro‐debromination reaction did not appreciably improve the relative ratio of labelled to unlabelled ester. The specific activity of the labelled 1,4‐benzodiazepine‐2‐one obtained from 1850 MBq [ 18 F]F − was found to be ≈37 MBq/μmol (1 mCi/μmol).