A one liter round bottom flask was charged with 5-chloro-4-hydroxypyridin-2(1H)-one (10 g, 68.7 mmol), t-butyl 4-hydroxypiperidine-1-carboxylate (16.59 g, 82 mmol), triphenylphosphine (27.0 g, 103 mmol) and DMF (200 ml). This mixture was stirred for 40 minutes to form a clear and homogeneous solution. The solution was then cooled to 0° C. and diisopropyl azodicarboxylate (16.23 mL, 82 mmol) was added drop-wise while maintaining the temperature below 20° C. during the addition. After the addition, the reaction mixture was allowed to warm to room temperature overnight. The reaction was then heated to 60° C. for 0.5 hours. After cooling the reaction mixture to room temperature, the DMF was distilled from the reaction under high vacuum at 50° C. to yield a brownish, viscous oil. The oil was dissolved in 300 mL of chloroform and then was washed with dilute sodium bicarbonate (pH 8-10) (3×50 mL) The chloroform layer was directly concentrated to afford a light yellow viscous oil, which was partitioned between 250 mL of diethyl ether and 70 mL of 1 N NaOH. The aqueous phase was extracted thoroughly with diethyl ether until LCMS showed no triphenylphosphine oxide or other impurities in the aqueous layer. The aqueous layer was purged with nitrogen to remove residual ether and then acidified slowly with 1 N HCl (˜70 mL) to pH 5 followed by cooling to 0° C. for 2 hours. The precipitates were collected by filtration, washed with ice water (2×20 mL), and air dried overnight. The light yellow solid was further vacuum dried at 40° C. to a constant weight to yield t-butyl 4-(5-chloro-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate (13.2 g, 40.1 mmol, 58.4% yield) as a light yellow solid. 1H-NMR (CDCl3, 400 MHz) δ 12.5 (br, s, 1H), 7.19 (s, 1H), 5.75 (s, 1H), 4.34-4.41 (m, 1H), 3.40-3.48 (m, 2H), 3.26-3.37 (m, 2H), 1.71-1.83 (m, 2H), 1.60-1.71 (m, 2H), 1.32 (s, 9H); MS m/e 329.3 (M+H+), 273.20 (M+H+-t-butyl).
