Rapid and efficient synthesis of stable isotope labeled [ 13 C 4 , D 4 ]‐5‐(hydroxymethyl)thiazole: versatile building block for biologically interesting compounds

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 13 C and four deuterium atoms in 32% total yield is reported. Condensation of [ 13 C 2 ]‐chloro acetic acid with [ 13 C]‐thiourea gave [ 13 C 3 ]‐2,4‐thiazolidinedione. Reaction of [ 13 C 3 ]‐2,4‐thiazolidinedione with phosphorus oxybromide and [ 13 C, D]‐DMF (Me 2 N 13 CDO) produced [ 13 C 4 , D]‐2,4‐dibromo‐thiazole‐5‐carboxaldehyde. The resultant aldehyde was then reduced by sodium borodeuteride to [ 13 C 4 , D 2 ]‐(2,4‐dibromo‐thiazol‐5‐yl)‐methanol. Catalytic deuteration of [ 13 C 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 [ 13 C 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. Copyright © 2009 John Wiley & Sons, Ltd.