Synthesis of (13C-Methoxy)Methacetin for Isotopic Breath Tests

Abstract

Asynthesis of (13C-methoxy)methacetin, one of the most important agents for liver function diagnosis by stable-isotope breath tests, was developed. It was based on O-alkylation of phenols by alkylhalides through an intermediate potassium salt of paracetamol [N-(4-hydroxyphenyl)acetamide]. The synthesis was carried out using 13C-methyliodide in the presence of K2CO3 in one step under mild conditions (20 – 25°C) with high selectivity to isolate the product in 97.8% yield, 99.6 mass% purity, and 99.1 at% isotopic purity. The physical properties were determined. Physicochemical analytical methods for (13C-methoxy)methacetin using NMR and IR spectroscopy and ESI-MS mass spectrometry were developed and could be used for quality control of the product during preparation for its mass production.