Hexane → (E)-5-methyl-2-[2-(1-naphthyl)-vinyl]-4-piperidinopyridine hydrochloride

Participants

Reaction Conditions

Reaction Steps

A suspension of 13.2 g (30.0 mmoles) of (1-naphthylmethyl)triphenylphosphonium chloride in 150 ml of tetrahydrofuran was cooled to about -30° C. in a cooling bath, and under a stream of nitrogen, 23.2 ml of a 1.55M hexane solution of n-butyllithium was added dropwise. The reaction mixture was further stirred at the above temperature for 0.5 hour, and a solution of 6.2 g (30.0 mmoles) of 5-methyl-4-piperidino-2-pyridinecarbaldehyde in 30 ml of tetrahydrofuran was added dropwise. After the addition, the cooling bath was removed, and the temperature was raised to room temperature. The mixture was further stirred at room temperature for 1 hour. Water (30 ml) was added to the reaction mixture, and tetrahydrofuran was evaporated under reduced pressure. The remaining aqueous layer was extracted with ether. The ether layer was washed with a saturated aqueous sodium chloride solution, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. Hexane (500 ml) was added to the residue. The precipitated triphenylphosphine oxide was removed by filtration, and the filtrate was concentrated under reduced pressure to give a crude mixture of (E)- and (Z)-5-methyl-2-[2-(1-naphthyl)vinyl]-4-piperidinopyridines. The crude mixture was purified by silic gel column chromatography (eluted with hexane/ethyl acetate=2/1). The resulting (E)- and (Z)-isomers were each treated with an ethanol solution of hydrogen chloride, and then recrystallized from methanol/ether to give 4.5 g (yield 41%) of the captioned compound (14-A) and 3.7 g (yield 37%) of the captioned compound (14-B) as crystals.

Provenance & Evidence