Acetic Acid → 2-(2-Amino-thiazol-5-ylmethylene)-malonic acid diethyl ester

Participants

Reaction Steps

To a solution of 2-amino-thiazole-5-carbaldehyde (47%; 6 g; 23 mmol) in CH2Cl2 (30 mL) and DMF (30 mL), was added 4A molecular sieves, diethyl malonate (3.5 mL; 23 mmol), piperidine (1.1 mL; 11.5 mmol) and acetic acid (0.7 mL; 11.5 mmol). The reaction mixture was stirred at room temperature for 96 hours. Then EtOAc was added, and the reaction mixture was filtered through celite in order to remove the precipitate formed. EtOAc (500 mL) was added to the filtrate, and the organic phase was washed with NaHCO3 and brine. The organic phase was dried and concentrated to yield 4.9 g of the crude product. Addition of petroleum ether to a solution of the crude product in ethanol followed by filtration afforded 2-(2-amino-thiazol-5-ylmethylene)-malonic acid diethyl ester (1.13 g, 18%).

Provenance & Evidence