Iodine → alpha,alpha-Bis(4-fluorophenyl)-1-(phenylmethyl)-4-piperidinemethanol

Participants

Reaction Steps

To a dry 2 liter round bottom flask containing magnesium turnings (6.08 g, 0.25 mole) and an iodine crystal in 600 ml of dry tetrahydrofuran (distilled from lithium aluminum hydride) and under an atmosphere of nitrogen was added, dropwise, a solution of 52.5 g (0.30 mole) of p-bromofluorobenzene in 125 ml of tetrahydrofuran. The temperature of the reaction mixture was kept below 10° C. by cooling in an ice-methanol bath. The mixture was stirred at room temperature for 1.5 hours. A solution of 1-(phenylmethyl)-4-piperidinecarboxylic acid ethyl ester (24.7 g, 0.1 mole) in tetrahydrofuran was added, and the mixture was stirred at room temperature for 17 hours. The reaction was poured into an icy, aqueous solution of ammonium chloride, and the resulting solution was extracted with methylene chloride. The methylene chloride solution was extracted with dilute sodium hydroxide and was dried (magnesium sulfate). The solvent was removed in vacuo to give an oil. This was crystallized from ether-hexane to give 19.87 g (51%) of the title compound, mp 113°-115° C.

Provenance & Evidence