Benzylamine → N-Benzyl-1-(4-methoxyphenyl)propan-2-amine (S)-2-hydroxy-2-phenylacetate

Participants

Reaction Conditions

Reaction Steps

To 800 mL of methanol were added 328 g of 4-methoxyphenylacetone (2 mol) and 214 g of N-benzylamine (2 mol). The imine formation was exothermic and the solution warmed to 45° C. After reaction was complete, the solution was hydrogenated at 50 psi for 6-8 hours in the presence of 3.3 g of 5% platinum on carbon catalyst. When the hydrogen uptake had stopped, the reaction was filtered through diatomaceous earth, and the filter cake was washed with 200 mL of methanol. The combined filtrates were placed in a 6-liter flask and diluted with 4.2 liters of methanol. (S)-L-Mandelic acid (304 g, 2 mol) was added and the mixture heated with stirring to reflux to obtain a clear solution. The solution was cooled to room temperature, stirred at room temperature for two hours and the mandelic acid salt filtered off. The recrystallization was repeated three times to obtain 60-70 g of the mandelic acid salt of the benzyl amine having an isomeric purity greater than 99.8% and a melting point of 164° C.

Provenance & Evidence