To a solution of (R)-3-(2-ethoxyphenoxy)piperidine (45 g, 204 mmol) and ethyl 2-chloropyrimidine-5-carboxylate (41.7 g, 224 mmol) in DMSO (300 mL) was added Et3N (40 mL, 305 mmol) at 20-25° C. The reaction mixture was heated to 100° C. for 2 hours, then was cooled to 20-25° C., diluted with H2O (300 mL) and extracted with EtOAc (3 times with 300 mL). The combined organic extracts were dried over Na2SO4, filtered, and concentrated to obtain ethyl (R)-2-(3-(2-ethoxyphenoxy)piperidin-1-yl)pyrimidine-5-carboxylate (71.5 g). MS (ES+) 372.3 (M+H).
