General procedure for the synthesis of ethyl 2-chlorothiazole-4-carboxylate from ethyl 2-aminothiazole-4-carboxylate: ethyl 2-aminothiazole-4-carboxylate (306 mg, 1.78 mmol) and cuprous chloride (CuCl, 238 mg, 2.4 mmol) were suspended in concentrated hydrochloric acid (8 mL). The mixture was cooled in a salt/ice bath. A solution of pre-cooled sodium nitrite (NaNO2, 166 mg, 2.4 mmol) in water (2 mL) was added slowly over 10 minutes. The reaction mixture was allowed to gradually warm up to room temperature over 1 h and stirring was continued for 1 h. The reaction mixture was allowed to warm up to room temperature over 1 h and stirring was continued for 1 h. Upon completion of the reaction, water was added to dilute it and the aqueous phase was extracted with ethyl acetate (EtOAc, 3 x 10 mL). The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate (Na2SO4), filtered and concentrated under reduced pressure to give the target product ethyl 2-chlorothiazole-4-carboxylate. Yield: 251 mg, 74% yield; liquid chromatography-mass spectrometry (LC/MS) retention time (tr) 1.06 min; mass spectrometry (electrospray positive ionization mode, ES+) m/z 192, 194 ([M+H]+); 1H NMR (250 MHz, CDCl3) δ 1.41 (t, 3H), 4.43 (q, 2H), 8.08 (s, 1H). 1H).
