Thioacetamide → Ethyl 2-methyl-1,3-thiazole-5-carboxylate

Participants

Reaction Conditions

Reaction Steps

Under nitrogen atmosphere, a solution of KOtBu (11.5 g) in THF (203 mL) was cooled to 0° C., and thereto were added dropwise ethyl chloroacetate (12.5 g) and ethyl formate (7.60 g) in THF (40 mL). After the addition, the mixture was stirred at 0° C. for 3 hours, and further stirred at room temperature for 16 hours. Water and a 6N aqueous hydrochloric acid solution were added to the mixture, and the mixture was extracted with Et2O, and dried over MgSO4. The solvent was evaporated under reduced pressure to give ethyl 2-chloroformyl-propionate. Under nitrogen atmosphere, to a solution of ethyl 2-chloroformylpropionate in acetone (250 mL) was added thioacetamide (7.74 g), and the mixture was stirred at 56° C. for 6 hours, and stirred at room temperature for 16 hours. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column (hexane/ethyl acetate=12.5/1→10/1) to give ethyl 2-methyl-1,3-thiazole-5-carboxylate (5.74 g, 32%).

Provenance & Evidence