2-Bromopyridine → alpha-(4-Fluorophenyl)-alpha-(2-pyridyl)-4-piperidinemethanol

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of 36.3 g (0.23 mole) of 2-bromopyridine in 500 ml of anhydrous tetrahydrofuran (THF) at -65° C. was added 88 ml (0.22 mole) of a commercial solution of 2.5M n-butyllithium in hexane at such a rate that the temperature did not exceed -60° C. The dark solution was stirred at -65° C. for 1 h and then treated dropwise with a solution of 24.9 g (0.1 mole) of 1-acetyl-4-(4-fluorobenzoyl)piperidine in 250 ml of THF at such a rate that the temperature did not exceed -60° C. The mixture was stirred for 1 h at -65° C. and overnight at ambient temperature. The dark mixture was poured into 2 L of a saturated ammonium chloride solution. The layers were separated and the aqueous layer was extracted once with a 500-ml portion of methylene chloride. The combined organic layers were washed successively with 500 ml of water, 500 ml of a 4% sodium hydroxide solution, 250 ml of water, and 250 ml brine.

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