Syntheses of deuterated phenylpropionic acid derivatives

2-(4-(2-Thienylhydroxymethyl)phenyl) propionic acid (I), 2-(4-carboxyphenyl) propionic acid (II), 2-(4-(5-hydroxy-2-thienylcarbonyl)phenyl)propionic acid (III) were labeled with multiple-deuterium for the purpose of using as internal standards in studies on the metabolism of 2-(4-(2-thienylcarbonyl)phenyl)propionic acid (suprofen, IV), anti-inflammatory agent, in man and animals by the mass fragmentography. I-d4 was obtained in a 93% yield from IV-d4 by reduction with sodium borohydride, and its deuterium content was 99 atom%. On the other hand, II-d4 (99 atom% D) was obtained by four-step synthesis from 2-((4-bromophenyl-d4)1, 1-ethyleneglycol)propane (V) in a 43% yield and III-d4 (98.4 atom% D) by five-step synthesis from V in a 12% yield.