883984-95-0

Step 2: Under nitrogen protection, 26 mL (173.4 mmol) of N,N,N',N'-tetramethylethylenediamine was dissolved in 180 mL of THF and cooled to -20°C. 70 mL (175 mmol) of a hexane solution of 2.5 M n-butyllithium was slowly added over 10 min. After stirring for 30 min, the reaction mixture was cooled to -78°C and 17.8 g (78.0 mmol) of tert-butyl (6-chloropyridin-2-yl)carbamate dissolved in 120 mL of THF was added dropwise over 20 min at this temperature. The reaction mixture was continued to be stirred at -78°C for 2.5 hours, followed by the dropwise addition of 27.2 g (116.7 mmol) of benzyl 4-oxopiperidine-1-carboxylate dissolved in a solution of 60 mL of THF over 10 minutes. After stirring at -78°C for 1 hour, the reaction mixture was gradually warmed to room temperature and then stirred at 40°C for 18 hours. Upon completion of the reaction, the reaction was quenched by dropwise addition of 150 mL of saturated sodium bicarbonate solution. The reaction mixture was extracted several times with dichloromethane, the organic phases were combined, washed with water, dried and concentrated. The residue was ground with petroleum ether/ethyl acetate (1:1) and the precipitate formed was collected by filtration, washed with petroleum ether/ethyl acetate (1:1) and dried. The product was obtained as 16.4 g in 54% yield. ESI-MS: m/z = 388 (M + H)+. HPLC retention time: 1.57 min (Method C).

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[2] Patent: US2011/172218, 2011, A1. Location in patent: Page/Page column 29-30
[3] Patent: US2012/149698, 2012, A1. Location in patent: Page/Page column 26
[4] Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 22, p. 6368 - 6372
[5] Patent: WO2006/41830, 2006, A2. Location in patent: Page/Page column 55