Butyric Acid → Ethyl 4-methyl-2-morpholin-4-yl-1,3-thiazole-5-carboxylate

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Reaction Steps

In a 100 mL round bottomed flask, to a solution of butanoic acid, 2-chloro-3-oxo-, ethyl ester (11.2 g, 68.4 mmol) in isopropyl alcohol (250 mL, 3300 mmol) was added morpholine-4-carbothioicacidamide (10.0 g, 68.4 mmol). The mixture was stirred at reflux for 1 hour, and then stirred at room temperature for 3 days. Volatiles were removed in vacuo, and the resulting residue was dissolved in ethyl acetate and diluted with saturated, aqueous sodium bicarbonate. The mixture was transferred to a separatory funnel, the layers were separated, and the organic layer dried with Na2SO4, filtered and concentrated in vacuo. The crude product was dissolved in DCM, adsorbed onto silica gel, and purified via column chromatography (120 g Isco column, gradient elution, 0-100% EtOAc/hexanes) to afford ethyl 4-methyl-2-(morpholin-4-yl)-1,3-thiazole-5-carboxylate (14.51 g, yield for 2 steps, 82%). LC/MS: (FA) ES+ 257, 259; 1H NMR (400 MHz, CDCl3) δ 4.26 (dd, J=7.1, 7.1, 2H), 3.87-3.67 (m, 4H), 3.59-3.42 (m, 4H), 2.55 (s, 3H), 1.33 (dd, J=7.1, 7.1, 3H).

Provenance & Evidence