(S)-mandelic acid → (-)-N-methyl-3-(2-methylphenoxy)-3-phenylpropylamine mandelic acid

Participants

Reaction Steps

To a solution of 33.69 g (0.132 mol) of (+-)-N-methyl-3-(2-methylphenoxy)-3-phenylpropylamine dissolved in 50 ml of diethyl ether was added a solution of 9.89 g (0.067 mol) of L-(+)-mandelic acid in 20 ml of warm xylene. The resulting mixture was refluxed gently for about 5 minutes and an additional 30 ml of diethyl ether was added thereto. The mixture was stirred at room temperature overnight and the resulting slurry was chilled in an ice bath. The mixture was filtered and the resulting solid was rinsed with 50 ml of diethyl ether. The solid was dissolved in 25 ml of methylene chloride and 50 ml of ethyl acetate and the resulting mixture was heated to reflux. The methylene chloride was removed by vacuum and 50 ml of diethyl ether was added to the residue. The mixture was seeded with a crystal of desired product and the resulting mixture was stirred for 2 hours while being chilled in an ice bath. The precipitated solid was collected by filtration and rinsed with 30 ml of a 1:1 (v:v) ethyl acetate/diethyl ether solvent solution. The resulting solid was dried overnight at 55° C. in a vacuum oven to provide 15.7 g of (-)-N-methyl-3-(2-methylphenoxy)-3-phenylpropylamine mandelic acid as an off white solid. mp =119°-122° C. The resulting solid was recrystallized with 50 ml of methanol employing 3 g of decolorizing carbon. The resulting mixture was filtered through Celite and the filtrate was concentrated under vacuum to provide a white solid. This solid was dissolved in 50 ml of ethyl acetate with heating and the solution was allowed to cool. An additional 50 ml of diethyl ether was added and the precipitated solid was collected by filtration and rinsed with 50 ml of 1:1 (v:v) ethyl acetate/diethyl ether. The solid was dried in a vacuum oven at 50° C. for 1 hour to provide 13.2 g of (-)-N-methyl-3-(2-methylphenoxy)-3-phenylpropylamine mandelic acid. mp=122°-123° C. Yield 49%.

Provenance & Evidence