Abstract
5-(Hydroxymethyl)thiazole is a versatile building block for many biologically active compounds. A rapid and efficient four-step synthesis of its stable isotope labeled counterpart with four C-13 and four deuterium atoms in 32% total yield is reported. Condensation of [C-13(2)]-chloro acetic acid with [C-13]-thiourea gave [C-13(3)]-2,4-thiazolidinedione. Reaction of [C-13(3)]-2,4-thiazolidinedione with phosphorus oxybromide and [C-13, D]-DMF ((Me2NCDO)-C-13) produced [C-13(4), D]-2,4-dibromothiazole-5-carboxaldehyde. The resultant aldehyde was then reduced by sodium borodeuteride to [C-13(4), D-2]-(2,4-dibromothiazol-5-yl)-methanol. Catalytic deuteration of [C-13(4), D-2]-(2,4-dibromo-thiazol-5-yl)-methanol by palladium black with deuterium gas at 1 atm pressure and room temperature produced completely de-brominated [C-13(4), D-4]-5-(hydroxymethyl)thiazole. De-bromination of the 2,4-dibromothiazole by the catalysis of palladium black provides a simple and convenient synthetic method for the stable isotope labeled and potentially radioactive isotope labeled thiazole compounds.