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Substitution‐reduction: an alternative process for the [ 18 F] N ‐(2‐fluoroethylation) of anilines
Author(s) -
Briard Emmanuelle,
Pike Victor W.
Publication year - 2004
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.816
Subject(s) - chemistry , nucleophilic substitution , aniline , medicinal chemistry , tetrahydrofuran , acetonitrile , salt (chemistry) , nitroethane , yield (engineering) , nuclear chemistry , inorganic chemistry , organic chemistry , solvent , nitromethane , materials science , metallurgy
Substitution of a halo atom (chloro or bromo) in easily prepared N ‐haloacetyl‐anilines with no‐carrier added (NCA) cyclotron‐produced [ 18 F]fluoride ion ( 18 F, t 1/2 = 109.8 min; β + =96.9%), followed by reduction with borane–tetrahydrofuran (BH 3 –THF), provides an alternative route to NCA [ 18 F] N ‐(2‐fluoroethyl)‐anilines. This two‐step and one‐pot process is rapid (∼50 min) and moderately high yielding (∼40% decay‐corrected radiochemical yield (RCY) overall). In the nucleophilic substitution reaction, 18‐crown‐6 is preferred to Kryptofix ® 222 as complexing agent for the solubilization of the counter‐ion (K + ), derived from an added metal salt, in acetonitrile. Weakly basic potassium bicarbonate is preferred as the added metal salt. Inclusion of a small amount of water, equating to 4–5 molar equivalents relative to 18‐crown‐6, base or precursor (held in equimolar ratio), is beneficial in preventing the adsorption of radioactivity onto the wall of the glass reaction vessel and for achieving high RCY in the nucleophilic substitution reaction. BH 3 –THF is effective for the rapid reduction of the generated [ 18 F] N ‐fluoroacetyl‐aniline to the [ 18 F] N ‐(2‐fluoroethyl)‐aniline. Copyright © 2004 John Wiley & Sons, Ltd.