Potassium Iodide → 1-(3-(Cyclopropylmethoxy)-4-fluorophenyl)ethanamine

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4-Fluoro-3-hydroxybenzoic acid (558 mg) was dissolved in DMF (5.0 mL). To the solution, (chloromethyl)cyclopropane (666 μL), potassium carbonate (990 mg), and potassium iodide (60 mg) were added, and the mixture was stirred at 90° C. for 6 hours. The reaction mixture was cooled to room temperature, water (10 mL) was then added thereto, and the resultant mixture was then extracted with toluene (10 mL). The organic layer was washed with brine (10 mL), dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. The residue was dissolved in toluene (4.0 mL). To the mixture, a solution of DIBAL in hexane (1.0 M, 7.6 mL) was then added dropwise at 0° C., and the reaction mixture was stirred at 0° C. for 2 hours. To the reaction mixture, water (1.0 mL) and an aqueous sodium hydroxide solution (1.0 M, 1.0 mL) were gradually added. The precipitate was removed by filtration and washed with ethyl acetate (10 mL×5). Then, the combined filtrate was concentrated under reduced pressure. To the residue, water (10 mL) was added, and the resultant mixture was then extracted with ethyl acetate (15 mL). The organic layer was washed with brine (10 mL), dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (40% ethyl acetate/hexane). The residue was dissolved in dichloromethane (10 mL). To the solution, manganese dioxide (5.0 g) was added at room temperature, and the mixture was heated to reflux at 45° C. for 6 hours. The reaction mixture was cooled to room temperature, and the precipitate was removed by filtration and washed with chloroform (15 mL×4). Then, the combined filtrate was concentrated under reduced pressure. The residue was dissolved in THF (3.0 mL). To the mixture, a solution of methylmagnesium bromide in THF (1.0 M, 1.4 mL) was added dropwise at 0° C., and the mixture was stirred at room temperature for 2 hours. To the reaction mixture, an aqueous saturated ammonium chloride solution (3.0 mL) was added at 0° C., and the resultant mixture was then extracted with ethyl acetate (10 mL×2). The organic layer was washed with brine (10 mL), dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. The obtained compound was dissolved in THF (5.0 mL). To the mixture, diphenylphosphoryl azide (650 μL) and DBU (494 μL) were added dropwise at room temperature, and the mixture was stirred for 1 hour. To the reaction mixture, brine (10 mL) was added, and the resultant mixture was then extracted with ethyl acetate (15 mL×2). The organic layer was washed with brine (10 mL), dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (20% ethyl acetate/hexane). The obtained compound was dissolved in methanol (5.5 mL). To the solution, 10% palladium-carbon (100 mg) was added, and the reaction mixture was stirred at room temperature for 2 hours under a hydrogen atmosphere. The precipitate was removed by filtration through a pad of Celite and washed with methanol (50 mL). Then, the combined filtrate was concentrated under reduced pressure to obtain the title compound (412 mg) as a crude product.

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