Tetrahydrofuran → 6,7-Dimethoxy-1-[(3,4-dimethoxyphenyl)methyl]-4-isoquinoline methanol

Participants

Reaction Steps

A slurry of 25.2 g of 6,7-dimethoxy-1-[(3,4-dimethoxyphenyl)methyl]-4-isoquinolinecarboxylic acid and 100 of dry tetrahydrofuran was stirred at 15° in an inert atmosphere while cautiously adding 200 ml of 1 molar borane/tetrahydrofuran complex. After stirring for 2 hours at room temperature, the initial solids had dissolved and were replaced by a second precipitate. The mixture was cautiously treated with 200 ml of water and the tetrahydrofuran was removed in vacuo at 40°. The chilled reaction mixture was then filtered, washed with water, and the damp stable borane complex was added portionwise with stirring to 200 ml of 2 N hydrochloric acid previously heated to 70°-80°. The resulting solution was heated an additional 15 minutes on the steam bath and was then chilled extracted with 100 ml of diethyl ether. The aqueous layer was added dropwise to 250 ml of cold 2 N sodium hydroxide with stirring. The resulting solids were removed by filtration, washed well with water, and dried to give 20.6 g of crude 6,7-dimethoxy-1[(3,4-dimethoxyphenyl)methyl]-4-isoquinoline methanol, mp 146°-148°. Recrystallization from methylene chloride/ethyl acetate gave 19.2 g of purified 6,7-dimethoxy-1-(3,4-dimethoxyphenyl)methyl]-4-isoquinoline methanol, mp 141°-143°.

Provenance & Evidence