4-BROMO-2-FORMYLTHIAZOLE

Synthesis

4394-85-8

4175-77-3

167366-05-4

GENERAL PROCEDURE: The reaction was carried out in a sealed tube under nitrogen atmosphere using tetrahydrofuran (4 mL) as solvent. To a solution of tert-butyl 2-bromothiazole-4-carboxylate (1a, 0.397 mmol) was slowly added isopropylmagnesium chloride/lithium chloride complex (1.3 M, 0.52 mmol) dropwise at -78 °C. After 15 min of reaction, the corresponding aldehyde (0.79-0.99 mmol) or N-formylmorpholine (used for the synthesis of 2-formylthiazoles 3a-b) was added dropwise with continuous stirring and the reaction mixture was continued to be stirred at -78°C for 10 min, followed by warming up to 0°C for 1.5 h of reaction. Upon completion of the reaction, the reaction was quenched by the addition of saturated aqueous ammonium chloride and the aqueous phase was extracted with ether (3 x 10 mL). The combined organic phases were washed sequentially with 5% aqueous hydrochloric acid (10 mL), saturated saline (10 mL), dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to remove the solvent. The crude product was purified by silica gel fast column chromatography using mixed solvent of ethyl acetate/petroleum ether as eluent (see below for the specific ratio) to obtain tert-butyl 2-(1-hydroxymethyl)thiazole-4-carboxylate derivatives (rac-2a-h).

References