Step 1: 4-hydroxypiperidine (1.93 g, 10 mmol), diisopropylethylamine (5.22 mL, 30 mmol), 5-bromo-2-chloropyrimidine (1.01 g, 10 mmol), and acetonitrile (50 mL) were added to a round-bottomed flask under nitrogen protection. The reaction mixture was heated to reflux for 15 hours and then concentrated under reduced pressure to remove the solvent. The crude product was dissolved in dichloromethane (150 mL), washed sequentially with water (2 x 20 mL), saturated saline (1 x 20 mL), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated under reduced pressure and purified by silica gel column chromatography to afford 1-(5-bromo-2-pyrimidinyl)-4-hydroxypiperidine (16) (2.55 g, 99% yield) as a white solid.1H NMR (400 MHz, DMSO-d6) δ: 8.34 (s, 2H), 4.73 (d, J = 4.0 Hz, 1H), 4.17-4.12 (m 2H), 3.74-3.68 (m, 1H), 3.28-3.22 (m, 2H), 1.76-1.70 (m, 2H), 1.33-1.25 (m, 2H); LCMS (ESI): m/z 260 [M+H]+.
