Sodium hydride → tert-Butyl 4-(3-(5-bromopyrimidin-2-yloxy)benzylidene)piperidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

Diethyl 3-(5-bromopyrimidin-2-yloxy)benzylphosphonate (0.700 g, 1.74 mmol) from Step 3 and 1,4,7,10,13-pentaoxacyclopentadecane (15-Crown-5, 0.017 mL, 0.087 mmol) were suspended in THF (2 mL). The mixture was cooled to 0° C. and sodium hydride (84 mg, 60% dispersion in mineral oil, 2.1 mmol) was added. The reaction was warmed to room temperature, stirred for 30 min and then cooled back to 0° C. A solution of 4-oxo-piperidine-1-carboxylic acid tert-butyl ester (0.452 g, 2.27 mmol) in THF (1.5 mL) was added and the reaction was warmed to room temperature. After 40 h, water was added and the mixture was extracted twice with ethyl acetate. The combined organic layers were washed with water, brine, dried over anhydrous sodium sulfate, filtered and concentrated to an orange oil (about 1 g). This material was purified by flash chromatography on silica (10-40% EtOAc:heptane) to afford the title compound (0.285 g, 37% yield). MS (APCI) M−100=346; 1H NMR (400 MHz, CDCl3) δ ppm 1.48 (s, 9H) 2.30-2.37 (m, 2H) 2.43-2.52 (m, 2H) 3.37-3.45 (m, 2H) 3.48-3.55 (m, 2H) 6.36 (s, 1H) 6.99-7.07 (m, 2H) 7.11 (d, J=7.80 Hz, 1H) 7.39 (t, J=7.90 Hz, 1H) 8.58 (s, 2H).

Provenance & Evidence