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Pd 0 ‐Mediated Cross‐Coupling of [ 11 C]Methyl Iodide with Carboxysilane for Synthesis of [ 11 C]Acetic Acid and its Active Esters: 11 C‐Acetylation of Small, Medium, and Large Molecules
Author(s) -
Doi Hisashi,
Goto Miki,
Sato Yuzuru
Publication year - 2021
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.202100638
Subject(s) - chemistry , tetrahydrofuran , methyl iodide , yield (engineering) , acetic acid , iodide , medicinal chemistry , cationic polymerization , catalysis , reagent , nuclear chemistry , radiochemistry , stereochemistry , organic chemistry , solvent , metallurgy , materials science
A rapid Pd 0 ‐mediated cross‐coupling of [ 11 C]CH 3 I with carboxytriphenylsilane ( 1 ) to synthesize [2‐ 11 C]acetic acid ([ 11 C] 2 ) and its corresponding imidyl esters as radiolabeling reagents for 11 C‐acetylation is reported. The reaction of [ 11 C]CH 3 I with 1 using a Pd 2 (dibenzylideneacetone) 3 /P( o ‐tolyl) 3 (1 : 4) catalyst in tetrahydrofuran/H 2 O (9 : 1) at 90 °C for 4 min afforded [ 11 C] 2 having satisfactory radioactivity and a good yield. The coupling of the cationic carbon atom of methyl iodide and the carboxyl group in 1 is an ionicity‐driven reversed‐polarity reaction. An injectable radiopharmaceutical formulation of [ 11 C] 2 prepared using 33 GBq of [ 11 C]CH 3 I had a radioactivity of 7.4–7.8 GBq, and the decay‐corrected radiochemical yield of [ 11 C]CH 3 I into [ 11 C] 2 was 63–73 %. [ 11 C] 2 was converted to [2‐ 11 C]acetic acid phthalimidyl ester ([ 11 C] 3 ) or its succinimidyl ester ([ 11 C] 10 ), which were used for the 11 C‐acetylation of 4‐aminophenol, oxytocin, and albumin. Injectable solutions of these products (0.25–2.0 GBq) are suitable for in vivo positron emission tomography studies.