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

Temperature

90 °C

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, J77.1, 7.1, 2H), 3.82-3.75 (m, 4H), 3.58-3.50 (m, 4H), 1.34 (dd, J=7.1, 7.1, 3H).

1. customat which point the vessel was sealed
2. temperaturethe mixture was heated
3. customReaction mixture
4. customtransferred to a separatory funnel
5. customLayers were separated
6. washthe organic layer was washed with water
7. dry with materialdried over Na2SO4
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. washResidue was subjected to column chromatography (gradient elution, 0 to 50% EA in hexanes)

ORD record

ord-cb47686ffc984188b48385b29dce38f4

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08796271B2