Efficient Synthesis of Molecular Precursors for Para‐Hydrogen‐Induced Polarization of Ethyl Acetate‐1‐13C and Beyond

Abstract

AbstractA scalable and versatile methodology for production of vinylated carboxylic compounds with 13C isotopic label in C1 position is described. It allowed synthesis of vinyl acetate‐1‐13C, which is a precursor for preparation of 13C hyperpolarized ethyl acetate‐1‐13C, which provides a convenient vehicle for potential in vivo delivery of hyperpolarized acetate to probe metabolism in living organisms. Kinetics of vinyl acetate molecular hydrogenation and polarization transfer from para‐hydrogen to 13C via magnetic field cycling were investigated. Nascent proton nuclear spin polarization (%PH) of ca. 3.3 % and carbon‐13 polarization (%P13C) of ca. 1.8 % were achieved in ethyl acetate utilizing 50 % para‐hydrogen corresponding to ca. 50 % polarization transfer efficiency. The use of nearly 100% para‐hydrogen and the improvements of %PH of para‐hydrogen‐nascent protons may enable production of 13C hyperpolarized contrast agents with %P13C of 20–50 % in seconds using this chemistry.