Synthesis
To a stirred solution of ethyl 2-chloro-3-oxopropanoate (5.0 g, 33 mmol) in benzene (50 mL) under argon protection was added thioacetamide (2.5 g, 33 mmol) and the mixture was heated to reflux. After 4 h, the reaction mixture was cooled to room temperature, diluted with water (50 mL) and neutralized with saturated sodium bicarbonate solution to pH 7. Subsequently, the reaction mixture was extracted with ethyl acetate and the organic phases were combined and washed sequentially with water and brine. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated in vacuum. Purification by silica gel column chromatography (eluent: heptane/ethyl acetate, 0 to 50% gradient) afforded ethyl 2-methylthiazole-5-carboxylate (2.68 g, 47% yield) as a yellow liquid. Mass spectrometry (MS) analysis showed: m/e = 172.0 [M + H]+.
References
[1] Journal of the American Chemical Society, 1982, vol. 104, # 16, p. 4461 - 4465
[2] Patent: WO2010/127974, 2010, A1. Location in patent: Page/Page column 43
[3] Patent: WO2018/53157, 2018, A1. Location in patent: Page/Page column 108; 109
[4] Patent: WO2018/160878, 2018, A1. Location in patent: Page/Page column 278-279
[5] Journal of Chemical Research, 2011, vol. 35, # 5, p. 313 - 316
