1,1'-Carbonyldiimidazole → 3-[3-fluoro-4-(4-oxo-3,4-dihydro-2H-pyridin-1-yl)phenyl]-2-oxo-5-oxazolidinecarboxylic acid ethyl ester

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Reaction Steps

CDI (162.0 mg, 1.0 mmol) is added with stirring to a solution of 3-[3-fluoro-4-(4-oxo-3,4-dihydro-2H-pyridin-1-yl)phenylamino]-2(R)-hydroxypropionic acid ethyl ester (Step 5, 146.0 mg, 0.45 mmol) in acetonitrile (4.0 mL), and the mixture is stirred at room temperature overnight. Solvent is removed under vacuum, and the residue partitioned between EtOAc (30 mL) and aq. 3% citric acid (30 mL). The aqueous layer is extracted with EtOAc (2×30 mL), and the combined organic layers are washed with water and saline and dried (MgSO4). EtOAc is removed under vacuum to afford the crude 3-[3-fluoro-4-(4-oxo-3,4-dihydro-2H-pyridin-1-yl)phenyl]-2-oxo-5-oxazolidinecarboxylic acid ethyl ester which is used in the next step w/o further purification (MS (m/z): 349 [M+H]+). The ester intermediate is taken up in 2M methanolic ammonia (8.0 mL, 16.0 mmol), and the resulting solution heated in a closed vial at 60° C. for 1 h. Volatiles are removed under vacuum, and the crude material purified by silica gel chromatography (eluent: 2% MeOH in CH2Cl2) to afford the title compound (55.0 mg, 38% for two steps) as white crystals, MS for C15H14FN3O4 m/z 320 (M+H)+; 1H NMR (CD3CN): δ 2.51 (m, 2 H), 3.89 (m, 2 H), 4.05 (m, 1 H), 4.24 (dd, 1 H), 4.97 (m, 1 H), 5.03 (d, 1 H), 6.18 (br. s, 1 H), 6.72 (br. s, 1 H), 7.20-7.40 (m, 3 H), 7.57 (d, 1 H).

Provenance & Evidence