4-bromo-2,3-difluorobenzaldehyde

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (4-Fluorophenyl)boronic acid (6.67 g), dicyclohexyl(2′,6′-dimethoxybiphenyl-2-yl)phosphine (1.96 g), a 2 M aqueous sodium carbonate solution (47.6 mL), and tris(dibenzylideneacetone)dipalladium(0) (2.04 g) were added at room temperature to a toluene (200 mL) solution of 4-bromo-2,3-difluorobenzaldehyde (7.02 g), and the mixture was stirred at 100° C. for 16 hours in an argon atmosphere. Water was added to the reaction mixture at room temperature, and the mixture was filtered through celite. Then, the filtrate was subjected to extraction with ethyl acetate. The obtained organic layer was washed with water and saturated saline in this order and dried over anhydrous magnesium sulfate, and then, the solvent was distilled off under reduced pressure. The obtained residue was passed through a short silica gel column (hexane/ethyl acetate), and the solvent was distilled off under reduced pressure. The obtained residue was crystallized (hexane/ethyl acetate) and further recrystallized (hexane/ethyl acetate) to obtain the title compound (6.01 g). the mixture was filtered through celite Then, the filtrate was subjected to extraction with ethyl acetate The obtained organic layer was washed with water and saturated saline in this order dried over anhydrous magnesium sulfate the solvent was distilled off under reduced pressure the solvent was distilled off under reduced pressure The obtained residue was crystallized (hexane/ethyl acetate) further recrystallized (hexane/ethyl acetate)

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (4-Fluorophenyl)boronic acid (6.67 g), dicyclohexyl(2′,6′-dimethoxybiphenyl-2-yl)phosphine (1.96 g), a 2 M aqueous sodium carbonate solution (47.6 mL), and tris(dibenzylideneacetone)dipalladium(0) (2.04 g) were added at room temperature to a toluene (200 mL) solution of 4-bromo-2,3-difluorobenzaldehyde (7.02 g), and the mixture was stirred at 100° C. for 16 hours in an argon atmosphere. Water was added to the reaction mixture at room temperature, and the mixture was filtered through celite. Then, the filtrate was subjected to extraction with ethyl acetate. The obtained organic layer was washed with water and saturated saline in this order and dried over anhydrous magnesium sulfate, and then, the solvent was distilled off under reduced pressure. The obtained residue was passed through a short silica gel column (hexane/ethyl acetate), and the solvent was distilled off under reduced pressure. The obtained residue was crystallized (hexane/ethyl acetate) and further recrystallized (hexane/ethyl acetate) to obtain the title compound (6.01 g). the mixture was filtered through celite Then, the filtrate was subjected to extraction with ethyl acetate The obtained organic layer was washed with water and saturated saline in this order dried over anhydrous magnesium sulfate the solvent was distilled off under reduced pressure the solvent was distilled off under reduced pressure The obtained residue was crystallized (hexane/ethyl acetate) further recrystallized (hexane/ethyl acetate)

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

Procedure: Sodium methoxide (28% methanol solution, 69.1 g) was added to a solution of 4-bromo-2,3-difluorobenzaldehyde (52.8 g) in methanol (600 mL) at room temperature. The mixture was refluxed under nitrogen atmosphere for 2 hours and concentrated in vacuo to about 1/4 volume. The mixture was diluted with ethyl acetate and water. The mixture was extracted with ethyl acetate. The organic layer was separated, washed with water and brine, dried over anhydrous magnesium sulfate and concentrated in vacuo to give the title compound (52.3 g). The mixture was refluxed under nitrogen atmosphere for 2 hours concentrated in vacuo to about 1/4 volume The mixture was diluted with ethyl acetate and water The mixture was extracted with ethyl acetate The organic layer was separated washed with water and brine dried over anhydrous magnesium sulfate concentrated in vacuo

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

Procedure: Sodium methoxide (28% methanol solution, 69.1 g) was added to a solution of 4-bromo-2,3-difluorobenzaldehyde (52.8 g) in methanol (600 mL) at room temperature. The mixture was refluxed under nitrogen atmosphere for 2 hours and concentrated in vacuo to about 1/4 volume. The mixture was diluted with ethyl acetate and water. The mixture was extracted with ethyl acetate. The organic layer was separated, washed with water and brine, dried over anhydrous magnesium sulfate and concentrated in vacuo to give the title compound (52.3 g). The mixture was refluxed under nitrogen atmosphere for 2 hours concentrated in vacuo to about 1/4 volume The mixture was diluted with ethyl acetate and water The mixture was extracted with ethyl acetate The organic layer was separated washed with water and brine dried over anhydrous magnesium sulfate concentrated in vacuo

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

Procedure: Sodium methoxide (28% methanol solution, 69.1 g) was added to a solution of 4-bromo-2,3-difluorobenzaldehyde (52.8 g) in methanol (600 mL) at room temperature. The mixture was refluxed under nitrogen atmosphere for 2 hours and concentrated in vacuo to about 1/4 volume. The mixture was diluted with ethyl acetate and water. The mixture was extracted with ethyl acetate. The organic layer was separated, washed with water and brine, dried over anhydrous magnesium sulfate and concentrated in vacuo to give the title compound (52.3 g). The mixture was refluxed under nitrogen atmosphere for 2 hours concentrated in vacuo to about 1/4 volume The mixture was diluted with ethyl acetate and water The mixture was extracted with ethyl acetate The organic layer was separated washed with water and brine dried over anhydrous magnesium sulfate concentrated in vacuo

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

Procedure: Sodium methoxide (28% methanol solution, 69.1 g) was added to a solution of 4-bromo-2,3-difluorobenzaldehyde (52.8 g) in methanol (600 mL) at room temperature. The mixture was refluxed under nitrogen atmosphere for 2 hours and concentrated in vacuo to about 1/4 volume. The mixture was diluted with ethyl acetate and water. The mixture was extracted with ethyl acetate. The organic layer was separated, washed with water and brine, dried over anhydrous magnesium sulfate and concentrated in vacuo to give the title compound (52.3 g). The mixture was refluxed under nitrogen atmosphere for 2 hours concentrated in vacuo to about 1/4 volume The mixture was diluted with ethyl acetate and water The mixture was extracted with ethyl acetate The organic layer was separated washed with water and brine dried over anhydrous magnesium sulfate concentrated in vacuo

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (2,4-Difluorophenyl)boronic acid (5.39 g), dicyclohexyl(2′,6′-dimethoxybiphenyl-2-yl)phosphine (1.40 g), a 2 M aqueous sodium carbonate solution (34.1 mL), and tris(dibenzylideneacetone)dipalladium(0) (1.46 g) were added at room temperature to a toluene (150 mL) solution of 4-bromo-2,3-difluorobenzaldehyde (5.03 g), and the mixture was stirred at 100° C. for 16 hours in a nitrogen atmosphere. Water was added to the reaction mixture at room temperature, and the mixture was filtered through celite. Then, the filtrate was subjected to extraction with ethyl acetate. The obtained organic layer was washed with water and saturated saline in this order and dried over anhydrous magnesium sulfate, and then, the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate) to obtain the title compound (5.49 g). the mixture was filtered through celite Then, the filtrate was subjected to extraction with ethyl acetate The obtained organic layer was washed with water and saturated saline in this order dried over anhydrous magnesium sulfate the solvent was distilled off under reduced pressure The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate)

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

Procedure: Sodium methoxide (28% methanol solution, 69.1 g) was added to a solution of 4-bromo-2,3-difluorobenzaldehyde (52.8 g) in methanol (600 mL) at room temperature. The mixture was refluxed under nitrogen atmosphere for 2 hours and concentrated in vacuo to about ¼ volume. The mixture was diluted with ethyl acetate and water. The mixture was extracted with ethyl acetate. The organic layer was separated, washed with water and brine, dried over anhydrous magnesium sulfate and concentrated in vacuo to give the title compound (52.3 g). The mixture was refluxed under nitrogen atmosphere for 2 hours concentrated in vacuo to about ¼ volume The mixture was diluted with ethyl acetate and water The mixture was extracted with ethyl acetate The organic layer was separated washed with water and brine dried over anhydrous magnesium sulfate concentrated in vacuo

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

Procedure: Sodium methoxide (28% methanol solution, 69.1 g) was added to a solution of 4-bromo-2,3-difluorobenzaldehyde (52.8 g) in methanol (600 mL) at room temperature. The mixture was refluxed under nitrogen atmosphere for 2 hours and concentrated in vacuo to about ¼ volume. The mixture was diluted with ethyl acetate and water. The mixture was extracted with ethyl acetate. The organic layer was separated, washed with water and brine, dried over anhydrous magnesium sulfate and concentrated in vacuo to give the title compound (52.3 g). The mixture was refluxed under nitrogen atmosphere for 2 hours concentrated in vacuo to about ¼ volume The mixture was diluted with ethyl acetate and water The mixture was extracted with ethyl acetate The organic layer was separated washed with water and brine dried over anhydrous magnesium sulfate concentrated in vacuo

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

Procedure: Cyclopropylboronic acid (1.77 g), a 2 M aqueous sodium carbonate solution (21 mL), tris(dibenzylideneacetone)dipalladium(0) (0.882 g), and dicyclohexyl(2′,6′-dimethoxybiphenyl-2-yl)phosphine (0.847 g) were added at room temperature to a toluene (70 mL) solution of 4-bromo-2,3-difluorobenzaldehyde (3.04 g), and the mixture was stirred at 100 C for 15 hours in an argon atmosphere. Water was added to the reaction mixture at room temperature, and the mixture was filtered through celite. Then, the filtrate was subjected to extraction with ethyl acetate. The obtained organic layer was washed with water and saturated saline in this order and dried over anhydrous magnesium sulfate, and then, the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate) to obtain the title compound (2.18 g). the mixture was filtered through celite Then, the filtrate was subjected to extraction with ethyl acetate The obtained organic layer was washed with water and saturated saline in this order dried over anhydrous magnesium sulfate the solvent was distilled off under reduced pressure The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate)

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

Procedure: Cyclopropylboronic acid (1.77 g), a 2 M aqueous sodium carbonate solution (21 mL), tris(dibenzylideneacetone)dipalladium(0) (0.882 g), and dicyclohexyl(2′,6′-dimethoxybiphenyl-2-yl)phosphine (0.847 g) were added at room temperature to a toluene (70 mL) solution of 4-bromo-2,3-difluorobenzaldehyde (3.04 g), and the mixture was stirred at 100 C for 15 hours in an argon atmosphere. Water was added to the reaction mixture at room temperature, and the mixture was filtered through celite. Then, the filtrate was subjected to extraction with ethyl acetate. The obtained organic layer was washed with water and saturated saline in this order and dried over anhydrous magnesium sulfate, and then, the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate) to obtain the title compound (2.18 g). the mixture was filtered through celite Then, the filtrate was subjected to extraction with ethyl acetate The obtained organic layer was washed with water and saturated saline in this order dried over anhydrous magnesium sulfate the solvent was distilled off under reduced pressure The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate)

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

Procedure: (2,4-Difluorophenyl)boronic acid (5.39 g), a 2 M aqueous sodium carbonate solution (34.1 mL), tris(dibenzylideneacetone)dipalladium(0) (1.46 g), and dicyclohexyl(2′,6′-dimethoxybiphenyl-2-yl)phosphine (1.40 g) were added at room temperature to a toluene (150 mL) solution of 4-bromo-2,3-difluorobenzaldehyde (5.03 g), and the mixture was stirred at 100 C for 16 hours in a nitrogen atmosphere. Water was added to the reaction mixture at room temperature, and the mixture was filtered through celite. Then, the filtrate was subjected to extraction with ethyl acetate. The organic layer was separated, washed with water and saturated saline in this order, and dried over anhydrous magnesium sulfate, and then, the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate) to obtain the title compound (5.49 g). the mixture was filtered through celite Then, the filtrate was subjected to extraction with ethyl acetate The organic layer was separated washed with water and saturated saline in this order dried over anhydrous magnesium sulfate the solvent was distilled off under reduced pressure The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate)