Tetrahydrofuran → Ethyl 4-bromo-2-morpholin-4-yl-1,3-thiazole-5-carboxylate

Participants

Reaction Conditions

Reaction Steps

In a sealable reaction vessel, to a suspension of ethyl 2,4-dibromo-1,3-thiazole-5-carboxylate (2.90 g, 9.21 mmol, prepared as in WO 2005026149) and cesium carbonate (9.00 g, 27.6 mmol) in tetrahydrofuran (24.3 mL, 299 mmol) was added morpholine (0.883 mL, 10.1 mmol), at which point the vessel was sealed and the mixture was heated with stirring at 90° C. for 4 hours. Reaction mixture was diluted with EtOAc and water and transferred to a separatory funnel. Layers were separated, and the organic layer was washed with water, dried over Na2SO4, filtered, and concentrated in vacuo. Residue was subjected to column chromatography (gradient elution, 0 to 50% EA in hexanes) to afford ethyl 4-bromo-2-morpholin-4-yl-1,3-thiazole-5-carboxylate (2.4 g, yield 81%) as a white solid. LC/MS: (FA) ES+ 321, 323; 1H NMR (300 MHz, CDCl3) δ 4.30 (dd, J=7.1, 7.1, 2H), 3.82-3.75 (m, 4H), 3.58-3.50 (m, 4H), 1.34 (dd, J=7.1, 7.1, 3H).

Provenance & Evidence