Abstract: A simple and convenient four-step synthesis of 4-hydroxy-2- trifluoromethylthiophene (1) a novel bioisostere of a, a, atrifluoro-m-cresol is reported. The key step is the condensation between ethyl 3-methoxy-4, 4, 4-trifluorocrotonate and methyl thioglycolate to form methyl 3-hydroxy-5-trifluoromethylthiophene-2-carboxylate (6). Hydrolysis of the ester followed by decarboxylation furnishes 1. Multi-hundred gram ...