4,5-diethoxy-3-fluorobenzene-1,2-dicarbonitrile

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:-22.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 4,5-diethoxy-3-fluorophthalonitrile (2.34 g, 10 mol) prepared in Preparation Example 1, sulfuric acid (0.56 mL, 10 mol), 20% palladium hydroxide-carbon (0.59 g, 50% hydrate) (20% palladium-carbon powder, palladium hydroxide type (hydrate), N.E. Chemical Corporation) and 1,2-dimethoxyethane (23 mL) was stirred at −22° C. under hydrogen atmosphere (atmospheric pressure) for 24 hours. After insoluble matter in the reaction mixture was filtered off, the residue was washed with methanol (23 mL) and the combined filtrate was divided into five equal portions. After one of them was concentrated at room temperature under reduced pressure, 1,2-dimethoxyethane (9.2 mL) was added thereto, and the mixture was stirred. Then, triethylamine (0.56 mL, 4 mol) was added dropwise thereto and the mixture was stirred at room temperature for one hour. Precipitated crystals were filtered, washed with a 5% methanol-1,2-dimethoxyethane solution, and dried at room temperature under reduced pressure to give 0.59 g of the ½ triethylamine solvate of the title compound (yield: 76%) as dark white crystals. After insoluble matter in the reaction mixture was filtered off the residue was washed with methanol (23 mL) After one of them was concentrated at room temperature under reduced pressure, 1,2-dimethoxyethane (9.2 mL) was added the mixture was stirred the mixture was stirred at room temperature for one hour Precipitated crystals were filtered washed with a 5% methanol-1,2-dimethoxyethane solution dried at room temperature under reduced pressure

反応条件: temp:-22.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 4,5-diethoxy-3-fluorophthalonitrile (2.34 g, 10 mol) prepared in Preparation Example 1, sulfuric acid (0.56 mL, 10 mol), 20% palladium hydroxide-carbon (0.59 g, 50% hydrate) (20% palladium-carbon powder, palladium hydroxide type (hydrate), N.E. Chemical Corporation) and 1,2-dimethoxyethane (23 mL) was stirred at −22° C. under hydrogen atmosphere (atmospheric pressure) for 24 hours. After insoluble matter in the reaction mixture was filtered off, the residue was washed with methanol (23 mL) and the combined filtrate was divided into five equal portions. After one of them was concentrated at room temperature under reduced pressure, 1,2-dimethoxyethane (9.2 mL) was added thereto, and the mixture was stirred. Then, triethylamine (0.56 mL, 4 mol) was added dropwise thereto and the mixture was stirred at room temperature for one hour. Precipitated crystals were filtered, washed with a 5% methanol-1,2-dimethoxyethane solution, and dried at room temperature under reduced pressure to give 0.59 g of the ½ triethylamine solvate of the title compound (yield: 76%) as dark white crystals. After insoluble matter in the reaction mixture was filtered off the residue was washed with methanol (23 mL) After one of them was concentrated at room temperature under reduced pressure, 1,2-dimethoxyethane (9.2 mL) was added the mixture was stirred the mixture was stirred at room temperature for one hour Precipitated crystals were filtered washed with a 5% methanol-1,2-dimethoxyethane solution dried at room temperature under reduced pressure

反応条件: temp:-23.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 4,5-diethoxy-3-fluorophthalonitrile (2.34 g, 10 mol) prepared in Preparation Example 1, sulfuric acid (0.56 mL, 10 mol), 20% palladium hydroxide-carbon (0.59 g, 50% hydrate) (20% palladium-carbon powder, palladium hydroxide type (hydrate), N.E. Chemical Corporation) and 1,2-dimethoxyethane (23 mL) was stirred at −23° C. under hydrogen atmosphere (atmospheric pressure) for 29 hours. After insoluble matter in the reaction mixture was filtered off, the residue was washed with methanol (23 mL), and the combined filtrate was divided into five equal portions. To one of them, triethylamine (0.14 mL, 1 mol) was added, and the mixture was stirred at 60° C. for three hours and concentrated at 40° C. under reduced pressure. Methanol (2.3 mL) and 1,2-dimethoxyethane (6.9 mL) were added to the residue, then sulfuric acid (0.11 mL, 2 mol) was added on ice, and the mixture was stirred. Precipitated crystals were filtered, washed with a 5% methanol-1,2-dimethoxyethane solution, and dried at room temperature under reduced pressure to give 0.45 g of the title compound (yield: 72%) as grayish white crystals. After insoluble matter in the reaction mixture was filtered off the residue was washed with methanol (23 mL) the mixture was stirred at 60° C. for three hours concentrated at 40° C. under reduced pressure Methanol (2.3 mL) and 1,2-dimethoxyethane (6.9 mL) were added to the residue the mixture was stirred Precipitated crystals were filtered washed with a 5% methanol-1,2-dimethoxyethane solution dried at room temperature under reduced pressure

反応条件: temp:-23.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 4,5-diethoxy-3-fluorophthalonitrile (2.34 g, 10 mol) prepared in Preparation Example 1, sulfuric acid (0.56 mL, 10 mol), 20% palladium hydroxide-carbon (0.59 g, 50% hydrate) (20% palladium-carbon powder, palladium hydroxide type (hydrate), N.E. Chemical Corporation) and 1,2-dimethoxyethane (23 mL) was stirred at −23° C. under hydrogen atmosphere (atmospheric pressure) for 29 hours. After insoluble matter in the reaction mixture was filtered off, the residue was washed with methanol (23 mL), and the combined filtrate was divided into five equal portions. To one of them, triethylamine (0.14 mL, 1 mol) was added, and the mixture was stirred at 60° C. for three hours and concentrated at 40° C. under reduced pressure. Methanol (2.3 mL) and 1,2-dimethoxyethane (6.9 mL) were added to the residue, then sulfuric acid (0.11 mL, 2 mol) was added on ice, and the mixture was stirred. Precipitated crystals were filtered, washed with a 5% methanol-1,2-dimethoxyethane solution, and dried at room temperature under reduced pressure to give 0.45 g of the title compound (yield: 72%) as grayish white crystals. After insoluble matter in the reaction mixture was filtered off the residue was washed with methanol (23 mL) the mixture was stirred at 60° C. for three hours concentrated at 40° C. under reduced pressure Methanol (2.3 mL) and 1,2-dimethoxyethane (6.9 mL) were added to the residue the mixture was stirred Precipitated crystals were filtered washed with a 5% methanol-1,2-dimethoxyethane solution dried at room temperature under reduced pressure

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

実験手順: After dissolving 4,5-diethoxy-3-fluorophthalonitrile (103 g) in ethyl acetate-ethanol-methanol (600 ml-600 ml-300 ml), platinum oxide (8 g) was added and the mixture was stirred at room temperature for 4 days under a hydrogen stream. The reaction mixture was filtered through celite, the organic layer was distilled off under reduced pressure and the residue was purified by silica gel column chromatography (solvent: n-hexane-ethyl acetate) to yield the title compound (21 g) as yellow crystals. was added The reaction mixture was filtered through celite the organic layer was distilled off under reduced pressure the residue was purified by silica gel column chromatography (solvent: n-hexane-ethyl acetate)

反応条件: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: After dissolving the 1,2-dibromo-4,5-diethoxy-3-fluorobenzene (480 g) in dimethylformamide (1400 ml), copper cyanide (345 g) was added and the mixture was stirred at 150° C. for 3 hours. Saturated aqueous ammonia was added to the reaction mixture, and then the mixture was stirred overnight and extraction was performed with toluene. The organic layer was dried over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure and the residue was purified by silica gel column chromatography (solvent: n-hexane-ethyl acetate) to yield the title compound (513 g) as white crystals. was added the mixture was stirred overnight extraction The organic layer was dried over anhydrous magnesium sulfate the solvent was distilled off under reduced pressure the residue was purified by silica gel column chromatography (solvent: n-hexane-ethyl acetate)

反応条件: temp:-22.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 4,5-diethoxy-3-fluorophthalonitrile (2.34 g, 10 mol) prepared in Preparation Example 1, sulfuric acid (0.56 mL, 10 mol), 20% palladium hydroxide-carbon (0.59 g, 50% hydrate) (20% palladium-carbon powder, palladium hydroxide type (hydrate), N.E. Chemical Corporation) and 1,2-dimethoxyethane (23 mL) was stirred at −22° C. under hydrogen atmosphere (atmospheric pressure) for 24 hours. After insoluble matter in the reaction mixture was filtered off, the residue was washed with methanol (23 mL) and the combined filtrate was divided into five equal portions. After one of them was concentrated at room temperature under reduced pressure, 1,2-dimethoxyethane (9.2 mL) was added thereto, and the mixture was stirred. Then, triethylamine (0.56 mL, 4 mol) was added dropwise thereto and the mixture was stirred at room temperature for one hour. Precipitated crystals were filtered, washed with a 5% methanol-1,2-dimethoxyethane solution, and dried at room temperature under reduced pressure to give 0.59 g of the ½ triethylamine solvate of the title compound (yield: 76%) as dark white crystals. After insoluble matter in the reaction mixture was filtered off the residue was washed with methanol (23 mL) After one of them was concentrated at room temperature under reduced pressure, 1,2-dimethoxyethane (9.2 mL) was added the mixture was stirred the mixture was stirred at room temperature for one hour Precipitated crystals were filtered washed with a 5% methanol-1,2-dimethoxyethane solution dried at room temperature under reduced pressure

反応条件: temp:-23.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 4,5-diethoxy-3-fluorophthalonitrile (2.34 g, 10 mol) prepared in Preparation Example 1, sulfuric acid (0.56 mL, 10 mol), 20% palladium hydroxide-carbon (0.59 g, 50% hydrate) (20% palladium-carbon powder, palladium hydroxide type (hydrate), N.E. Chemical Corporation) and 1,2-dimethoxyethane (23 mL) was stirred at −23° C. under hydrogen atmosphere (atmospheric pressure) for 29 hours. After insoluble matter in the reaction mixture was filtered off, the residue was washed with methanol (23 mL), and the combined filtrate was divided into five equal portions. To one of them, triethylamine (0.14 mL, 1 mol) was added, and the mixture was stirred at 60° C. for three hours and concentrated at 40° C. under reduced pressure. Methanol (2.3 mL) and 1,2-dimethoxyethane (6.9 mL) were added to the residue, then sulfuric acid (0.11 mL, 2 mol) was added on ice, and the mixture was stirred. Precipitated crystals were filtered, washed with a 5% methanol-1,2-dimethoxyethane solution, and dried at room temperature under reduced pressure to give 0.45 g of the title compound (yield: 72%) as grayish white crystals. After insoluble matter in the reaction mixture was filtered off the residue was washed with methanol (23 mL) the mixture was stirred at 60° C. for three hours concentrated at 40° C. under reduced pressure Methanol (2.3 mL) and 1,2-dimethoxyethane (6.9 mL) were added to the residue the mixture was stirred Precipitated crystals were filtered washed with a 5% methanol-1,2-dimethoxyethane solution dried at room temperature under reduced pressure