1(2H)-Naphthalenone, 3,4-dihydro-2-((dimethylamino)methyl)- → alpha-(2-dimethylaminomethyl-1,2,3,4-tetrahydro-1-hydroxy-1-naphthyl)-N-methyl-o-toluamide

Participants

Reaction Conditions

Reaction Steps

To a flask equipped with a stirrer, dropping funnel, condenser and gas inlet tube maintained under a nitrogen atmosphere there is added at room temperature 40.0 g (0.28 mole) of o-methyl-N-methyl benzamide and 250 ml. of anhydrous tetrahydrofuran. The reaction flask is immersed in an ice bath and cooled to an internal temperature of 5°C. Stirring is initiated and 380 ml. of 1.6 m. n-butyllithium (0.616 mole) in hexane is added dropwise in ca. 1 hour maintaining the temperature below 8°C. The resulting red dilithio salt is stirred at 5°C. for 1 additional hour and the reaction flask is then immersed in a dry-ice acetone bath and cooled to an internal temperature of -60°C. To the cold reaction mixture a solution of 56.8 g. (0.28 mole) of 2-(dimethylaminomethyl)-3,4-dihydro-1-(2H)-naphthalenone in 140 ml. of anhydrous tetrahydrofuran is added dropwise in ca. 45 min. maintaining the temperature between -60°C and -50° C. The resulting reaction mixture is stirred at -60°C. for 1 hour, allowed to warm to 0°C in ca 1 hour, and then treated with 200 ml. of saturated aqueous ammonium chloride while maintaining the temperature below 10°C. The resulting two layers are separated and the tetrahydrofuran layer is dried over magnesium sulfate, filtered and evaporated. The residue is chromatographed on silica gel with benzene; ethylacetate (1:1) to provide α-(2-dimethylaminomethyl-1,2,3,4-tetrahydro-1-hydroxy-1-naphthyl)-N-methyl-o-toluamide.

Provenance & Evidence