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A 500 mL 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 vacuum at 50° C. to yield 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 LC/MS 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 (M+H+), 273 (M+H+-t-butyl).

1. customto form a clear and homogeneous solution
2. temperaturewhile maintaining the temperature below 20° C.
3. additionduring the addition
4. additionAfter the addition
5. temperatureto warm to room temperature overnight
6. temperatureThe reaction was then heated to 60° C. for 0.5 hours
7. temperatureAfter cooling the reaction mixture to room temperature
8. distillationthe DMF was distilled from the reaction under vacuum at 50° C.
9. customto yield brownish
10. washwas washed with dilute sodium bicarbonate (pH 8-10) (3×50 mL)
11. concentrationThe chloroform layer was directly concentrated
12. customto afford a light yellow viscous oil, which
13. customwas partitioned between 250 mL of diethyl ether and 70 mL of 1 N NaOH
14. extractionThe aqueous phase was extracted thoroughly with diethyl ether until LC/MS
15. customThe aqueous layer was purged with nitrogen
16. customto remove residual ether
17. temperatureby cooling to 0° C. for 2 hours
18. filtrationThe precipitates were collected by filtration
19. washwashed with ice water (2×20 mL), and air
20. customdried overnight
21. customdried at 40° C. to a constant weight