Sodium hydride → Tert-butyl 4-{[(5-bromopyrimidin-2-yl)oxy]methyl}piperidine-1-carboxylate

Participants

Reaction Steps

A solution of N-Boc-4-piperidinemethanol (1.0 g, 4.50 mmol) in DMSO (2 mL) was added dropwise to a suspension of NaH (60% in mineral oil, 0.27 g, 6.76 mmol) in DMSO (4 mL). The mixture was stirred at ambient temperature for 1 h, then 30 minutes at 50° C. Cooled to ambient temperature, a solution of 5-bromo-2-iodopyrimidine (1.38 g, 4.73 mmol) in DMSO (4 mL) was added dropwise, and the reaction mixture was stirred at ambient temperature overnight, then heated at 100° C. for 5 h. Cooled to ambient temperature, the mixture was poured in water, extracted with EtOAc. The organic extract was washed with water and brine, dried over Na2SO4, filtered, and the filtrate was concentrated to give the crude product as a dark brown oil. The crude product was purified by chromatography on ISCO silica gel column eluted with a EtOAc:hexane gradient (hexane to 15% EtOAc) to give 0.455 g (28%) of 1,1-dimethylethyl 4-{[(5-bromo-2-pyrimidinyl)oxy]methyl}-1-piperidinecarboxylate as a white solid. 1H NMR (400 MHz, CDCl3): δ 8.51 (s, 2H), 4.20-4.10 (m, 4H), 2.80-2.65 (m, 2H), 2.05-1.95 (m, 1H), 1.90-1.75 (m, 2H), 1.45 (s, 9H), 1.35-1.20 (m, 2H); LRMS (ESI), m/z 372/374 (M+H).

Provenance & Evidence