Benzaldehyde → 2-Cyclohexyl-1-(pyridin-2-YL)ethanamine

Participants

Reaction Steps

Under a nitrogen atmosphere, 1.365 kg (12.86 moles) of benzaldehyde was added with stirring and cooling to 1.39 kg (12.86 moles) of 2-(aminomethyl)pyridine maintaining the temperature <50° C. After stirring for 2-4 hours, the mixture was diluted with 13 L oft-butylmethyl ether (MTBE). To the clear solution was added 1.05 kg (27.72 moles) sodium hydroxide (flakes) and 2.375 kg (6.43 moles) of tetrabutylammonium iodide. The suspension was stirred for 2 hrs., then 2.3 kg (12.86 moles) of cyclohexylmethyl bromide was added. The reaction mixture was refluxed for 36-48 hrs. After cooling the mixture, it was diluted with 3 L of water followed by 12 L of 3N hydrochloric acid and stirred for 2-6 hours. The organic phase was separated and discarded. The aqueous phase was washed four times with 3 L of methylene chloride, then basified with 2.5 L of 0.5N ammonium hydroxide solution. The racemic amine was extracted three times with 4 L of methylene chloride, dried over sodium sulfate and concentrated to dryness. The oil product was stirred with 2 L of hexane, filtered and concentrated to yield 1.14 kg (43.5%) of 1-(R,S)-(2-pyridyl)-2-cyclohexylethylamine.

Provenance & Evidence