5-bromo-1,2-diethoxy-3-fluorobenzene

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 5-bromo-1,2-diethoxy-3-fluorobenzene (40.0 g, 0.15 mol) in acetic acid (200 mL), sodium acetate (16.2 g, 0.20 mol) and bromine (31.6 g, 0.20 mol) were added sequentially at room temperature, and the mixture was stirred at 50° C. for 1.5 hours. The reaction mixture was cooled to room temperature, and a saturated aqueous solution of sodium thiosulfate (400 mL) and water (400 mL) were added sequentially. The mixture was extracted once with heptane (800 mL) and three times with heptane (400 mL). The organic layer was washed sequentially with water (400 mL), once with a 2 N aqueous solution of sodium hydroxide (200 mL), once with a 2 N aqueous solution of sodium hydroxide (100 mL), and water (400 mL), then dried over anhydrous magnesium sulfate. The solvent was distilled off from the organic layer under reduced pressure and the residue was filtered. The filtrate was then purified by silica gel column chromatography (hexane, ethyl acetate) to give 52.0 g of the title compound (yield:quant.). The reaction mixture was cooled to room temperature The mixture was extracted once with heptane (800 mL) and three times with heptane (400 mL) The organic layer was washed sequentially with water (400 mL), once with a 2 N aqueous solution of sodium hydroxide (200 mL), once with a 2 N aqueous solution of sodium hydroxide (100 mL), and water (400 mL) dried over anhydrous magnesium sulfate The solvent was distilled off from the organic layer under reduced pressure the residue was filtered The filtrate was then purified by silica gel column chromatography (hexane, ethyl acetate)

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 5-bromo-1,2-diethoxy-3-fluorobenzene (40.0 g, 0.15 mol) in acetic acid (200 mL), sodium acetate (16.2 g, 0.20 mol) and bromine (31.6 g, 0.20 mol) were added sequentially at room temperature, and the mixture was stirred at 50° C. for 1.5 hours. The reaction mixture was cooled to room temperature, and a saturated aqueous solution of sodium thiosulfate (400 mL) and water (400 mL) were added sequentially. The mixture was extracted once with heptane (800 mL) and three times with heptane (400 mL). The organic layer was washed sequentially with water (400 mL), once with a 2 N aqueous solution of sodium hydroxide (200 mL), once with a 2 N aqueous solution of sodium hydroxide (100 mL), and water (400 mL), then dried over anhydrous magnesium sulfate. The solvent was distilled off from the organic layer under reduced pressure and the residue was filtered. The filtrate was then purified by silica gel column chromatography (hexane, ethyl acetate) to give 52.0 g of the title compound (yield:quant.). The reaction mixture was cooled to room temperature The mixture was extracted once with heptane (800 mL) and three times with heptane (400 mL) The organic layer was washed sequentially with water (400 mL), once with a 2 N aqueous solution of sodium hydroxide (200 mL), once with a 2 N aqueous solution of sodium hydroxide (100 mL), and water (400 mL) dried over anhydrous magnesium sulfate The solvent was distilled off from the organic layer under reduced pressure the residue was filtered The filtrate was then purified by silica gel column chromatography (hexane, ethyl acetate)

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

Procedure: To a solution of 5-bromo-3-fluorobenzene-1,2-diol (37.5 g, 0.18 mol) in N,N-dimethylformamide (DMF) (375 mL), ethyl iodide (58.0 mL, 0.72 mol) and potassium carbonate (62.6 g, 0.45 mol) were added sequentially under a nitrogen atmosphere, the mixture was stirred at room temperature for 30 minutes, and then stirred at 50° C. for 16.5 hours. The reaction mixture was cooled to room temperature and water (1.0 L) was added thereto. The mixture was extracted once with ethyl acetate (1.0 L) and twice with ethyl acetate (500 mL). Water (1.0 L) was added to the organic layer and the mixture was filtered through celite. After separating the filtrate, the organic layer was washed sequentially with water (1.0 L), twice with a 5 N aqueous solution of sodium hydroxide (200 mL), and saturated saline. The organic layer was dried over anhydrous magnesium sulfate and the solvent was distilled off under reduced pressure. The resultant residue was purified by silica gel column chromatography (hexane, ethyl acetate) to give 41.7 g of the title compound (yield: 87%). stirred at 50° C. for 16.5 hours The reaction mixture was cooled to room temperature The mixture was extracted once with ethyl acetate (1.0 L) and twice with ethyl acetate (500 mL) Water (1.0 L) was added to the organic layer the mixture was filtered through celite After separating the filtrate the organic layer was washed sequentially with water (1.0 L), twice with a 5 N aqueous solution of sodium hydroxide (200 mL), and saturated saline The organic layer was dried over anhydrous magnesium sulfate the solvent was distilled off under reduced pressure The resultant 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: To a solution of 5-bromo-3-fluorobenzene-1,2-diol (37.5 g, 0.18 mol) in N,N-dimethylformamide (DMF) (375 mL), ethyl iodide (58.0 mL, 0.72 mol) and potassium carbonate (62.6 g, 0.45 mol) were added sequentially under a nitrogen atmosphere, the mixture was stirred at room temperature for 30 minutes, and then stirred at 50° C. for 16.5 hours. The reaction mixture was cooled to room temperature and water (1.0 L) was added thereto. The mixture was extracted once with ethyl acetate (1.0 L) and twice with ethyl acetate (500 mL). Water (1.0 L) was added to the organic layer and the mixture was filtered through celite. After separating the filtrate, the organic layer was washed sequentially with water (1.0 L), twice with a 5 N aqueous solution of sodium hydroxide (200 mL), and saturated saline. The organic layer was dried over anhydrous magnesium sulfate and the solvent was distilled off under reduced pressure. The resultant residue was purified by silica gel column chromatography (hexane, ethyl acetate) to give 41.7 g of the title compound (yield: 87%). stirred at 50° C. for 16.5 hours The reaction mixture was cooled to room temperature The mixture was extracted once with ethyl acetate (1.0 L) and twice with ethyl acetate (500 mL) Water (1.0 L) was added to the organic layer the mixture was filtered through celite After separating the filtrate the organic layer was washed sequentially with water (1.0 L), twice with a 5 N aqueous solution of sodium hydroxide (200 mL), and saturated saline The organic layer was dried over anhydrous magnesium sulfate the solvent was distilled off under reduced pressure The resultant residue was purified by silica gel column chromatography (hexane, ethyl acetate)