Sodium hydride → HCID 49657818, compound

Participants

Reaction Steps

A solution of N-Boc-4-piperidinemethanol (1.0 g, 4.50 mmol) was added dropwise to a suspension of NaH (60% in mineral oil, 0.27 g, 6.76 mmol) in DMSO (2 mL). The mixture was stirred at ambient temperature for 1 h, then 30 minutes at 50° C. The mixture was cooled to ambient temperature and a solution of 3,6-dichloropyridazine (0.73 g, 4.73 mmol) in DMSO (4 mL) was added dropwise, and the reaction mixture was stirred at ambient temperature overnight, poured onto water, then extracted with EtOAc, washed with water and brine, dried over Na2SO4, filtered, and the filtrate was concentrated to give the crude product as a dark reddish brown oil. The crude product was purified by chromatography on ISCO silica gel column eluted with a EtOAc:hexane gradient (0 to 30%) to give 0.85 g (56%) of 1,1-dimethylethyl 4-{[(6-chloro-3-pyridazinyl)oxy]methyl}-1-piperidinecarboxylate as a white solid. 1H NMR (400 MHz, CDCl3): δ 7.36 (d, 1H, J=9.0 Hz), 6.94 (d, 1H, J=9.1 Hz), 4.34 (d, 2H, J=6.6 Hz), 4.20-4.10 (m, 2H), 2.80-2.65 (m, 2H), 2.10-1.95 (m, 1H), 1.85-1.70 (m, 2H), 1.45 (s, 9H), 1.35-1.20 (m, 2H); LRMS (ESI), m/z 328 (M+H).

Provenance & Evidence