1,1'-Carbonyldiimidazole → ethyl (5R)-3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinecarboxylate

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Reaction Steps

A solution of 3-fluoro-4-morpholinoaniline (J. Med. Chem. 1996, 39(3), 673-679, 0.796 g, 4.0 mmol), ethyl 2(R)-epoxypropanoate (0.696 g, 6.0 mmol) and lithium triflate (0.97 g, 6.2 mmol) in acetonitrile (12 mL) was stirred at 50-60° C. overnight. Solvent and excess epoxide was removed under reduced pressure, and the crude amino alcohol was redissolved in dry acetonitrile (40 mL) and 1,1′-carbonyldiimidazole (1.46 g, 9.0 mmol) was added. The mixture was stirred at ambient temperature overnight, and then the solvent was removed under reduced pressure. The residue was partitioned between ethyl acetate (70 mL) and 3% aqueous citric acid (100 mL), the layers are separated, and the organic phase was washed with 3% aqueous citric acid (3×100 mL), water and saline, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The product mixture was then purified by silica gel chromatography, eluting with ethanol/methylene chloride (2/98), and the appropriate fractions are pooled and concentrated to give the title compound, MS (ESI+) for C16H19N2O5F m/z 339 (M+H)+.

Provenance & Evidence