Hydrochloric Acid → 1-[4-Fluoro-3-(tert-butoxycarbonylamino)phenyl]-2-(5-fluoro-2-methoxyphenyl)-2-methyl-1-propanone

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A mixture of 1-[4-fluoro-3-(tert-butoxycarbonyl -amino)phenyl]-2-methyl-1-propanone (0.11 g), 2-bromo-4-fluoroanisole (0.057 mL), palladium(II) acetate (4.5 mg), tri(tert-butyl)phosphine tetrafluoroborate (5.8 mg) and sodium tert-butoxide (96 mg) in tetrahydrofuran (1 mL) was stirred at 70° C. under an argon atmosphere for 3 days. To the reaction mixture was added water, and the mixture was stirred for 10 minutes. The mixture was poured into 1 mol/L hydrochloric acid, and the resulting mixture was extracted with ethyl acetate. The extract was washed with water and brine successively, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=10/1) to give 1-[4-fluoro-3-(tert-butoxycarbonylamino)phenyl]-2-(5-fluoro -2-methoxyphenyl)-2-methyl-1-propanone (45 mg). This material was dissolved in hydrochloric acid (4 mol/L ethyl acetate solution, 3 mL), and the mixture was stirred at room temperature overnight. The reaction mixture was poured into a saturated aqueous sodium hydrogen carbonate solution, and the resulting mixture was extracted with ethyl acetate. The extract was washed with brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on aminopropylated silica gel (eluent: n-hexane/ethyl acetate=4/1 -3/1) to give the title compound (25 mg).

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