Hydrochloric Acid → Methyl 3-oxo-5-(1,3-thiazole-2-yl)-4-pentenoate

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Reaction Steps

Methyl 3-oxo-5-(1,3-thiazole-2-yl)-4-pentenoate was prepared from 3-(1,3-thazol-2-yl)-2-propenoic acid (Bull. Chem. Soc. Jap. 1974, 47, 151.) according to the literature procedure (Heterocycles 1994, 38, 751.). To a stirred solution of 3-(1,3-thiazol-2-yl)-2-propenoic acid (100.0 g, 644.4 mmol) in DMF (1000 ml) was added 1,1′-carbonyldiimidazole (115.0 g, 708.9 mmol) in small portions. After stirring at room temperature for 5 hours, to the reaction mixture were added anhydrous magnesium chloride (73.6 g, 773.0 mmol) and monomethyl malonate potassium salt (120.8 g, 773.0 mmol). The resulting suspension was heated at 55° C. with stirring for 14 h. After cooling to room temperature, the reaction mixture was poured into 1500 ml of 2 N HCl, and extracted with a mixture of EtOAc (1500 ml) and toluene (500 ml). The organic phase was separated and the aqueous phase was extracted with a 3:1 mixture of EtOAc and toluene (2000 ml). The combined organic phase was washed with H2O (1000 ml) and brine (1000 ml), dried (Na2SO4) and evaporated to afford 132.0 g of methyl 3-oxo-5-(1,3-thiazole-2-yl)-4-pentenoate (1/2 of keto/enol form)

Provenance & Evidence