Dimethyl Sulfoxide → Tert-butyl 4-(2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

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Reaction Conditions

Reaction Steps

A 250 mL round bottom flask was charged with 4-hydroxypyridin-2(1H)-one (6.13 g, 55.1 mmol), tert-butyl 4-(methylsulfonyloxy)piperidine-1-carboxylate (12.83 g, 45.9 mmol) (prepared according to the procedure described in patent application WO-2009/012275), K2CO3 (14.60 g, 106 mmol) and DMSO (56 mL). The mixture was heated to 100° C. for 3 hours and then allowed to cool to room temperature overnight. The resulting mixture was diluted with H2O (300 mL) and extracted with EtOAc (2×150 mL). The organic layers were combined and concentrated in vacuo to a white solid. The solid was purified by flash chromatography (SiO2, 0-100% EtOAc in CH2Cl2 and then SiO2, 0-10% MeOH in CH2Cl2) to yield tert-butyl 4-(2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate (6.05 g, 45% yield) as a white solid. 1H NMR (400 MHz, CHLOROFORM-d) δ 12.34 (br. s., 1H) 7.21 (d, J=7.28 Hz, 1H) 5.96 (dd, J=7.28, 2.51 Hz, 1H) 5.87 (d, J=2.26 Hz, 1H) 4.35-4.58 (m, 1H) 3.59-3.80 (m, 2H) 3.17-3.41 (m, 2H) 1.87-2.08 (m, 2H) 1.65-1.87 (m, 2H) 1.47 (s, 9H). MS (ESI) 295 (M+H).

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