Water → tert-Butyl 4-(3-(3-methylpyridin-2-yloxy)benzylidene)piperidine-1-carboxylate

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Reaction Steps

Diethyl 3-(3-methylpyridin-2-yloxy)benzylphosphonate (4.3 g, 13 mmol) from Step 3 and 1,4,7,10,13-pentaoxacyclopentadecane (15-Crown-5, 0.05 mL, 0.28 mmol) were combined in THF (150 mL). Sodium hydride (564 mg, 60% dispersion in mineral oil, 14.1 mmol) was added. The reaction was stirred for 30 min and then a solution of 4-oxo-piperidine-1-carboxylic acid tert-butyl ester (1.81 g, 14.1 mmol) in THF (15 mL) was added. After 16 h, water was added and the layers were separated. The aqueous layer was extracted with EtOAc (2×200 mL) and the combined organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by silica gel chromatography (10-30%, EtOAc:heptane) to afford the title compound (3.9 g, 80% yield) as a thick oil.

Provenance & Evidence