Triethylamine → Tert-butyl 4-[1-hydroxy-3-(6-methylpyridin-2-yl)prop-2-ynyl]piperidine-1-carboxylate

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Reaction Steps

A mixture of zinc trifluoromethanesulfonate (0.07 g, 0.19 mmol) and triethylamine (0.065 mL, 0.47 mmol) in anhydrous toluene (5 mL) was stirred at room temperature under nitrogen atmosphere. After 1 h, 2-ethynyl-6-methyl-pyridine (0.13 g, 1.13 mmol) prepared as described in WO200544267 was added and after 15 min was dropped a solution of 1-Boc-4-piperidinecarboxaldehyde (0.2 g, 0.938 mmol) in toluene (1 mL): the resulting mixture was heated at 100° C. for 6 h. Afterwards, it was cooled to r.t., diluted with water and extracted with EtOAc. The combined organic layers were washed with brine, dried on Na2SO4 and evaporated to dryness in vacuo to give a crude, which was purified twice by automated flash liquid chromatography (Horizon™-Biotage) eluting with CHCl3-MeOH 98-2 affording the title product (0.13 g) as a brown oil.

Provenance & Evidence