Formic Acid → 6-Methoxy-3,4-dihydroisoquinoline

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Reaction Steps

In tetrahydrofuran (100 ml), 3-methoxyphenethylamine (75.0 g) was dissolved, followed by the addition of formic acid (60 ml) and acetic anhydride (108 ml) under ice cooling. The resulting mixture was stirred overnight at room temperature. A saturated aqueous solution of sodium bicarbonate was added to the reaction mixture. The organic lay-layer so separated was washed with saturated saline and dried over anhydrous sodium sulfate. The residue obtained by distilling off the solvent under reduced pressure was dissolved in benzene (200 ml), followed by the dropwise addition of phosphorus oxychloride (140 ml) under ice cooling. After stirring at 70° C. for 15 minutes, ice and then 2N hydrochloric acid were added. The resulting mixture was stirred under ice cooling for one hour. The water layer was separated and neutralized with potassium carbonate. After extraction with dichloromethane, the extract was dried over anhydrous sodium sulfate. The residue obtained by distilling off the solvent under reduced pressure was purified by chromatography on a silica gel column (dichloromethane˜dichloromethane:methanol=100:1), the title compound (13.5 g, 17%) was obtained.

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