tert-butyl N-(5-bromo-2-fluorophenyl)carbamate

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4-bromo-2-(tert-butoxycarbonylamino)-1-fluorobenzene (0.57 g), trimethylsilylacetylene (0.55 mL), tetrakis(triphenylphosphine)palladium(0) (23 mg)and copper (I) iodide (7 mg) in N,N-diisopropylamine (5.7 mL) was stirred at 80° C. overnight. The reaction mixture was cooled to room temperature, and the mixture was diluted with diethyl ether. The insoluble material was removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=15/1) to give 1-(tert-butoxy -carbonylamino)-2-fluoro-5-trimethylsilylethynylbenzene (0.6 g). This material was dissolved in tetrahydrofuran (10 mL). To the solution was added tetra(n-butyl)ammonium fluoride (1 mol/L tetrahydrofuran solution, 2.4 mL), and the mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=20/1 -10/1) to give the title compound (0.34 g). The reaction mixture was cooled to room temperature The insoluble material was removed by filtration the filtrate was concentrated under reduced pressure The residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=15/1)

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 1-(2-methoxyphenyl)-2-methyl-1-propanone (0.58 g), 4-bromo-2-(tert-butoxycarbonylamino)-1-fluoro -benzene (0.94 g), palladium(II) acetate (37 mg), tri(tert -butyl)phosphine tetrafluoroborate (47 mg) and sodium tert-butoxide (0.78 g) in tetrahydrofuran (10 mL) was stirred at 60° C. under an argon atmosphere overnight. 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 diethyl ether. 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=95/5−85/15) to give 2-[3-(tert-butoxycarbonylamino)-4-fluorophenyl]-1-(2-methoxyphenyl)-2-methyl-1-propanone (0.91 g). To the obtained 2-[3-(tert-butoxycarbonylamino)-4-fluorophenyl]-1-(2-methoxyphenyl)-2-methyl-1-propanone (0.34 g) was added hydrochloric acid (4 mol/L ethyl acetate solution, 3 mL), and the mixture was stirred at room temperature for 3 hours. 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 dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure to give the title compound (0.22 g). the mixture was stirred for 10 minutes the resulting mixture was extracted with diethyl ether The extract was washed with water and brine successively dried over anhydrous sodium sulfate The solvent was removed under reduced pressure the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=95/5−85/15)

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4-bromo-2-(tert-butoxycarbonylamino)-1-fluorobenzene (0.57 g), trimethylsilylacetylene (0.55 mL), tetrakis(triphenylphosphine)palladium(0) (23 mg)and copper (I) iodide (7 mg) in N,N-diisopropylamine (5.7 mL) was stirred at 80° C. overnight. The reaction mixture was cooled to room temperature, and the mixture was diluted with diethyl ether. The insoluble material was removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=15/1) to give 1-(tert-butoxy -carbonylamino)-2-fluoro-5-trimethylsilylethynylbenzene (0.6 g). This material was dissolved in tetrahydrofuran (10 mL). To the solution was added tetra(n-butyl)ammonium fluoride (1 mol/L tetrahydrofuran solution, 2.4 mL), and the mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=20/1 -10/1) to give the title compound (0.34 g). The reaction mixture was cooled to room temperature The insoluble material was removed by filtration the filtrate was concentrated under reduced pressure The residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=15/1)

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 1-(2-methoxyphenyl)-2-methyl-1-propanone (0.58 g), 4-bromo-2-(tert-butoxycarbonylamino)-1-fluoro -benzene (0.94 g), palladium(II) acetate (37 mg), tri(tert -butyl)phosphine tetrafluoroborate (47 mg) and sodium tert-butoxide (0.78 g) in tetrahydrofuran (10 mL) was stirred at 60° C. under an argon atmosphere overnight. 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 diethyl ether. 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=95/5−85/15) to give 2-[3-(tert-butoxycarbonylamino)-4-fluorophenyl]-1-(2-methoxyphenyl)-2-methyl-1-propanone (0.91 g). To the obtained 2-[3-(tert-butoxycarbonylamino)-4-fluorophenyl]-1-(2-methoxyphenyl)-2-methyl-1-propanone (0.34 g) was added hydrochloric acid (4 mol/L ethyl acetate solution, 3 mL), and the mixture was stirred at room temperature for 3 hours. 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 dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure to give the title compound (0.22 g). the mixture was stirred for 10 minutes the resulting mixture was extracted with diethyl ether The extract was washed with water and brine successively dried over anhydrous sodium sulfate The solvent was removed under reduced pressure the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=95/5−85/15)