Dimethylformamide → Tert-butyl 4-(1-(4-cyano-2-fluorophenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

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Reaction Steps

To a mixture of tert-butyl 4-(2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate (730 mg, 2.480 mmol, Step A of Example 132) and DMF (12 mL) at room temperature was added sodium hydride (114 mg, 2.85 mmol). After stirring at room temperature for 1 hr, 3,4-difluorobenzonitrile (345 mg, 2.480 mmol, Aldrich) was added and the reaction mixture was heated at 100° C. for 1.5 hrs and cooled to room temperature. The resulting mixture was diluted with EtOAc and water and the aqueous layer was extracted further with EtOAc (3×). The combined organic extracts were washed with water and brine, dried (MgSO4) and evaporated under reduced pressure. The residue was purified by flash chromatography on silica gel (0-100% EtOAc in hexanes) to give the title compound (602.4 mg, 58.7%) as an off-white solid. 1H NMR (500 MHz, CDCl3) δ 7.47-7.64 (m, 3H), 7.10 (d, J=7.70 Hz, 1H), 6.04 (dd, J=7.70, 2.20 Hz, 1H), 5.96 (d, J=2.20 Hz, 1H), 4.41-4.55 (m, 1H), 3.65-3.80 (m, 2H), 3.27-3.39 (m, 2H), 1.91-2.04 (m, 2H), 1.71-1.84 (m, 2H), 1.48 (s, 9H). MS (ESI) 358 (M+H−C4H8).

Provenance & Evidence