ethyl 4-bromo-2-fluorobenzoate

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: Sodium (1.815 g, 78.9 mmol, Aldrich) was cut into small pieces and added to ethanol (100 mL). After all the pieces were dissolved, the clear solution was added to a solution of ethyl 4-bromo-2-fluoro-benzoate (13 g, 52.6 mmol) in ethanol (20 mL) cooled to 0° C. The ice bath was then removed and the mixture was stirred at room temperature for 12 h. The reaction mixture was concentrated in vacuo, and the residue was taken in water and 20% ethyl acetate-hexane. The organic layer was washed with saturated solution of sodium bicarbonate, brine, and dried over anhydrous sodium sulfate. The solids were filtered off, and the filtrate was concentrated in vacuo. Purification of the crude residue by flash chromatography (120 g of silica gel, eluting with 10-15% ethyl acetate in hexane) gave 4-bromo-2-ethoxy-benzoic acid ethyl ester as white solids (11.020 g, 77%). After all the pieces were dissolved The ice bath was then removed The reaction mixture was concentrated in vacuo The organic layer was washed with saturated solution of sodium bicarbonate, brine dried over anhydrous sodium sulfate The solids were filtered off the filtrate was concentrated in vacuo Purification of the crude residue by flash chromatography (120 g of silica gel, eluting with 10-15% ethyl acetate in hexane)

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

実験手順: Sodium (1.815 g, 78.9 mmol, Aldrich) was cut into small pieces and added to ethanol (100 mL). After all the pieces were dissolved, the clear solution was added to a solution of ethyl 4-bromo-2-fluoro-benzoate (13 g, 52.6 mmol) in ethanol (20 mL) cooled to 0° C. The ice bath was then removed and the mixture was stirred at room temperature for 12 h. The reaction mixture was concentrated in vacuo, and the residue was taken in water and 20% ethyl acetate-hexane. The organic layer was washed with saturated solution of sodium bicarbonate, brine, and dried over anhydrous sodium sulfate. The solids were filtered off, and the filtrate was concentrated in vacuo. Purification of the crude residue by flash chromatography (120 g of silica gel, eluting with 10-15% ethyl acetate in hexane) gave 4-bromo-2-ethoxy-benzoic acid ethyl ester as white solids (11.020 g, 77%). After all the pieces were dissolved The ice bath was then removed The reaction mixture was concentrated in vacuo The organic layer was washed with saturated solution of sodium bicarbonate, brine dried over anhydrous sodium sulfate The solids were filtered off the filtrate was concentrated in vacuo Purification of the crude residue by flash chromatography (120 g of silica gel, eluting with 10-15% ethyl acetate in hexane)

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 4-bromo-2-fluorobenzoic acid (3.0 g) in ethanol (20 mL) was added thionyl chloride (2.0 mL) at 0° C., and the mixture was stirred overnight at 70° C. To the reaction mixture was added saturated aqueous sodium hydrogencarbonate solution, the mixture was concentrated under reduced pressure, and the residue was extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give the title compound (3.30 g). the mixture was concentrated under reduced pressure the residue was extracted with ethyl acetate The organic layer was washed successively with water and saturated brine dried over anhydrous magnesium sulfate concentrated under reduced pressure

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 4-bromo-2-fluorobenzoic acid (3.0 g) in ethanol (20 mL) was added thionyl chloride (2.0 mL) at 0° C., and the mixture was stirred overnight at 70° C. To the reaction mixture was added saturated aqueous sodium hydrogencarbonate solution, the mixture was concentrated under reduced pressure, and the residue was extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give the title compound (3.30 g). the mixture was concentrated under reduced pressure the residue was extracted with ethyl acetate The organic layer was washed successively with water and saturated brine dried over anhydrous magnesium sulfate concentrated under reduced pressure

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

実験手順: 1.0 g ethyl 4-bromo-2-fluorobenzoate, 0.56 g 2-nitroaniline, 1.85 g cesium carbonate, 37 mg tris(dibenzylideneacetone)-dipalladium (0), 38 mg 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (racemic mixture) and 15 mL toluene were stirred at 100° C. for 24 hours under nitrogen atmosphere. Water was added thereto, then the reaction mixture was extracted with ether, and the organic layer was dried over sodium sulfate. After the solvent was evaporated, the residue was purified by NH silica gel chromatography (ethyl acetate/hexane). By recrystallization from ethyl acetate/hexane, 0.95 g of the title compound was obtained as yellow crystals. the reaction mixture was extracted with ether the organic layer was dried over sodium sulfate After the solvent was evaporated the residue was purified by NH silica gel chromatography (ethyl acetate/hexane) By recrystallization from ethyl acetate/hexane