Water → 6,7-Dimethoxy-1-(4-(trifluoromethyl)phenethyl)-3,4-dihydroisoquinoline

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Reaction Steps

Phosphorous oxychloride (4.77 g, 2.9 mL, 31.0 mmol, 2.2 eq) was added to a suspension of 44a (5.37 g, 14.1 mmol, 1.0 eq) in acetonitrile (100 mL) resulting in the formation of a clear solution. The mixture was heated at reflux for 3.5 h. The resulting yellow solution was cooled to rt and concentrated under reduced pressure to a thick yellow oil. The oil was dissolved in methanol (10 mL) and water (100 mL) was added slowly with stirring. After several minutes, a thick suspension formed. The mixture was made alkaline by the slow addition of saturated sodium bicarbonate solution, adding water (˜100 mL) to facilitate stirring. The thick white suspension was extracted with ethyl acetate (1×200 mL, 1×100 mL). The combined organic solution was washed with brine (100 mL), dried over sodium sulfate, filtered and the filtrate concentrated under reduced pressure to give 5.12 g (100%) of 45a as an off-white solid.

Provenance & Evidence