methyl 2-chlorothiazole-5-carboxylate

726185-57-5

72605-86-8

A suspension was prepared from methyl 2-aminothiazole-5-carboxylate hydrochloride (14.0 g, 71.927 mmol) in 8 ml of concentrated hydrochloric acid to which 20 g of crushed ice was added. An aqueous solution (30 ml) of sodium nitrite (5.0 g, 72.464 mmol) was added slowly and dropwise under external cooling conditions, ensuring that the reaction temperature was maintained below 0 °C at all times. After 30 min of reaction, copper(I) chloride (7.2 g, 72.735 mmol) was added and stirring was continued under cooling conditions for 1 h, followed by a slow warming up to room temperature over 1.5 h. The reaction was completed with the addition of ether. After completion of the reaction, the reaction mixture was thoroughly extracted with ether, the organic phases were combined, washed with saturated brine solution, dried over anhydrous sodium sulfate and the solvent was subsequently evaporated. Methyl 2-chlorothiazole-5-carboxylate 4.3 g (34% yield) was obtained as a colorless oil with a thin layer chromatographic Rf value of 0.94 (Unfolding agent: EI D). The product was used directly in the next reaction without further purification. Mass spectrometry analysis showed the molecular ion peak M+ = 177/179 (Cl isotope peak).