1-(4-bromo-3-fluorophenyl)ethanone

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 4-bromo-3-fluoro-N-methoxy-N-methylbenzamide (58.5 g, 0.223 mol) in tetrahydrofuran (500 mL) was added 3.00 M of methylmagnesium chloride in tetrahydrofuran (125 mL, 0.38 mol) at 0° C. The mixture was stirred for 1 h at 0° C., and was quenched with cold saturated NH4Cl solution (150 mL). The organic layer was separated and concentrated under reduced pressure. The residue was diluted with ethyl acetate (100 mL). The aqueous layer was diluted with water (100 mL) and was extract with ethyl acetate (3×50 mL). The organic solution and extracts were combined, washed with brine, dried over MgSO4, filtered, and concentrated under reduced pressure to give product (48.4 g, 99%) which was directly used in next step without further purification. was quenched with cold saturated NH4Cl solution (150 mL) The organic layer was separated concentrated under reduced pressure The residue was diluted with ethyl acetate (100 mL) The aqueous layer was diluted with water (100 mL) was extract with ethyl acetate (3×50 mL) washed with brine dried over MgSO4 filtered concentrated under reduced pressure

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 4-bromo-3-fluoro-N-methoxy-N-methylbenzamide (58.5 g, 0.223 mol) in tetrahydrofuran (500 mL) was added 3.00 M of methylmagnesium chloride in tetrahydrofuran (125 mL, 0.38 mol) at 0° C. The mixture was stirred for 1 h at 0° C., and was quenched with cold saturated NH4Cl solution (150 mL). The organic layer was separated and concentrated under reduced pressure. The residue was diluted with ethyl acetate (100 mL). The aqueous layer was diluted with water (100 mL) and was extract with ethyl acetate (3×50 mL). The organic solution and extracts were combined, washed with brine, dried over MgSO4, filtered, and concentrated under reduced pressure to give product (48.4 g, 99%) which was directly used in next step without further purification. was quenched with cold saturated NH4Cl solution (150 mL) The organic layer was separated concentrated under reduced pressure The residue was diluted with ethyl acetate (100 mL) The aqueous layer was diluted with water (100 mL) was extract with ethyl acetate (3×50 mL) washed with brine dried over MgSO4 filtered concentrated under reduced pressure

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 4-bromo-3-fluoro-N-methoxy-N-methylbenzamide (58.5 g, 0.223 mol) in tetrahydrofuran (500 mL) was added 3.00 M of methylmagnesium chloride in tetrahydrofuran (125 mL, 0.38 mol) at 0° C. The mixture was stirred for 1 h at 0° C., and was quenched with cold saturated NH4Cl solution (150 mL). The organic layer was separated and concentrated under reduced pressure. The residue was diluted with ethyl acetate (100 mL). The aqueous layer was diluted with water (100 mL) and was extract with ethyl acetate (3×50 mL). The organic solution and extracts were combined, washed with brine, dried over MgSO4, filtered, and concentrated under reduced pressure to give product (48.4 g, 99%) which was directly used in next step without further purification. was quenched with cold saturated NH4Cl solution (150 mL) The organic layer was separated concentrated under reduced pressure The residue was diluted with ethyl acetate (100 mL) The aqueous layer was diluted with water (100 mL) was extract with ethyl acetate (3×50 mL) washed with brine dried over MgSO4 filtered concentrated under reduced pressure

反応条件: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: N,N,N′,N′-Tetramethylethylenediamine (0.667 mL, 4.42 mmol), zinc cyanide (1.46 g, 12.4 mmol), tris(dibenzylideneacetone)dipalladium(0) (54.05 mg, 0.059 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (124.3 mg, 0.215 mmol) was added successively to a solution of 1-(4-bromo-3-fluorophenyl)ethanone (4.34 g, 20.0 mmol) in N,N-dimethylformamide (15 mL) in a microwave tube. The tube was sealed and degassed three times, and heated to 160° C. under microwave irradiation with a 240 s hold time, and 300 Watt maximum power input. After cooling, the reaction mixture was filtered through a pad of Celite with a thin layer of silica gel in the middle using dichloromethane as the eluant. The combined filtrates were concentrated under reduced pressure. The residue was purified by chromatography on silica gel with ethyl acetate in hexanes (0-40%) to give the desired product. (3.20 g, 98.1%). The tube was sealed degassed three times After cooling the reaction mixture was filtered through a pad of Celite with a thin layer of silica gel in the middle The combined filtrates were concentrated under reduced pressure The residue was purified by chromatography on silica gel with ethyl acetate in hexanes (0-40%)

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 4-bromo-3-fluoro-N-methoxy-N-methylbenzamide (58.5 g, 223 mmol) in tetrahydrofuran (500 mL) was added 3M of methylmagnesium chloride in THF (125 mL, 380 mmol) at 0° C. The reaction mixture was stirred for 1 hour at 0° C., and was quenched with cold aqueous ammonium chloride solution (150 mL). The organic layer was separated and concentrated under reduced pressure. The residue was redissolved in ethyl acetate (100 mL). The aqueous layer was diluted with water (100 mL) and was extracted with ethyl acetate (3×50 mL). The organic extracts were combined, washed with brine, and dried over magnesium sulfate. Filtration and concentration under reduced pressure gave the product (48.4 g) which was used in the next reaction step without further purification. was quenched with cold aqueous ammonium chloride solution (150 mL) The organic layer was separated concentrated under reduced pressure The residue was redissolved in ethyl acetate (100 mL) The aqueous layer was diluted with water (100 mL) was extracted with ethyl acetate (3×50 mL) washed with brine dried over magnesium sulfate Filtration and concentration under reduced pressure

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 4-bromo-3-fluoro-N-methoxy-N-methylbenzamide (Step 1, 58.5 g, 223 mmol) in tetrahydrofuran (500 mL) was added 3M of methylmagnesium chloride in THF (125 mL, 380 mmol) at 0° C. The reaction mixture was stirred for 1 hour at 0° C., and was quenched with cold aqueous ammonium chloride solution (150 mL). The organic layer was separated and concentrated under reduced pressure. The residue was re-dissolved in ethyl acetate (100 mL). The aqueous layer was diluted with water (100 mL) and was extracted with ethyl acetate (3×50 mL). The organic extracts were combined, washed with brine, and dried over magnesium sulfate. Filtration and concentration under reduced pressure gave the product (48.4 g) which was used in the next reaction step without further purification. was quenched with cold aqueous ammonium chloride solution (150 mL) The organic layer was separated concentrated under reduced pressure The residue was re-dissolved in ethyl acetate (100 mL) The aqueous layer was diluted with water (100 mL) was extracted with ethyl acetate (3×50 mL) washed with brine dried over magnesium sulfate Filtration and concentration under reduced pressure

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 4-bromo-3-fluoro-N-methoxy-N-methylbenzamide (Step 1, 58.5 g, 223 mmol) in tetrahydrofuran (500 mL) was added 3M of methylmagnesium chloride in THF (125 mL, 380 mmol) at 0° C. The reaction mixture was stirred for 1 hour at 0° C., and was quenched with cold aqueous ammonium chloride solution (150 mL). The organic layer was separated and concentrated under reduced pressure. The residue was re-dissolved in ethyl acetate (100 mL). The aqueous layer was diluted with water (100 mL) and was extracted with ethyl acetate (3×50 mL). The organic extracts were combined, washed with brine, and dried over magnesium sulfate. Filtration and concentration under reduced pressure gave the product (48.4 g) which was used in the next reaction step without further purification. was quenched with cold aqueous ammonium chloride solution (150 mL) The organic layer was separated concentrated under reduced pressure The residue was re-dissolved in ethyl acetate (100 mL) The aqueous layer was diluted with water (100 mL) was extracted with ethyl acetate (3×50 mL) washed with brine dried over magnesium sulfate Filtration and concentration under reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of crude 1-(4-bromo-3-fluorophenyl)ethanol oil (from Step 1) in DCM (100 mL) was added pyridinium dichromate (8.96 g, 23.82 mmol). The mixture was stirred overnight at room temperature. To the mixture was added celite, the reaction mixture was filtered through a celite pad and rinsed several times with DCM. The filtrate was concentrated under reduced pressure. The crude material was purified by column chromatography [SiO2, 40 g, heptane/ethyl acetate] providing 1-(4-bromo-3-fluorophenyl)ethanone (3.08 g) as a white solid. To the mixture was added celite the reaction mixture was filtered through a celite pad rinsed several times with DCM The filtrate was concentrated under reduced pressure The crude material was purified by column chromatography [SiO2, 40 g, heptane/ethyl acetate]

反応条件: temp:0.00; pressure:0.00; stir: