Synthesis of optically active 2-(4-(2-thienylcarbonyl)-phenyl)propionic acid labeled with deuterium

2-(4-(2-Thienylcarbonyl)phenyl)propionic acid (suprofen), an anti-inflammatory agent, was labeled with multiple-deuterium for the purpose of investigating the metabolism in man and animals by the ion cluster technique. Racemic suprofen-d4 was prepared by ten-stop synthesis from bromobenzene-d5 in a 32% yield, and its deuterium content was 99 atom%. This racemic suprofen-d4 was resolved by use of an optically active alpha-methylbenzylamine, resulting that optically active suprofen-d4 was obtained in a 11% yield and was 96.5 atom% D. On the other hand, suprofen-d7 (99 atom% D) was obtained by five-step synthesis from toulene-d8 and methyl-d3 iodide in a 24% yield.