2-fluoro-6-methoxybenzonitrile

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: At 50° C. and under a nitrogen blanket, a solution of 0.273 mol of sodium pyrazolide (prepared from equimolar amounts of pyrazole and sodium hydride) in 140 ml of N,N-dimethylethyleneurea is dripped into a solution of 41,2 g (0.273 mol) of 2-methoxy-6-fluorobenzonitrile (preparation: J. Heterocycl. Chem., 25, 1173, 1988) in 50 mi of N, N-dimethylethyleneurea, and the mixture is stirred for 2 hours at 60° C. The batch is cooled and stirred into 4 liters of ice water, and the crystals which precipitate are suction filtered and dried; there is obtained 37.1 g of the product of m.p. 93°-94° C. At 50° C. The batch is cooled filtered dried

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

実験手順: A mixture of 2-fluoro-6-methoxybenzonitrile (15.94 g, 105.5 mmol) and a solution of methyl magnesium iodide in diethyl ether (3 M, 46.0 cm3, 137 mmol) was heated to 100° C. for 18 h. Upon cooling to room temperature, aqueous hydrochloric acid (3 M, 94 cm3) was added and the mixture was heated to reflux to for 4 h. When the reaction had cooled to room temperature the organic layer was separated and the aqueous phase was extracted with ethyl acetate (100 cm3). The combined organic extracts were washed with brine (100 cm3) before being dried (Na2SO4). The solvent was removed in vacuo to afford the title compound as an oil (117.7 g, 100%). the mixture was heated to reflux to for 4 h When the reaction had cooled to room temperature the organic layer was separated the aqueous phase was extracted with ethyl acetate (100 cm3) The combined organic extracts were washed with brine (100 cm3) before being dried (Na2SO4) The solvent was removed in vacuo

反応条件: temp:190.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 151 g (1 mol) of 2-fluoro-6-methoxybenzonitrile and 346.5 g (3 mol) of pyridinium hydrochloride were introduced into a 2 l flask and then slowly heated to 190° C. under a protective gas atmosphere and then stirred at this temperature for 5 h. The mixture was cooled by slowly stirring to room temperature overnight. Then 1000 ml of water were added, and the mixture was heated to 80° C. After adding 1000 ml of methyl tert.-butyl ether, the phases were separated and the aqueous phase was back-extracted twice with 500 ml of methyl tert.-butyl ether. The combined methyl tert.-butyl ether phases were washed once with 800 ml of 10% strength aqueous sodium hydroxide solution and once with 400 ml of water. The two aqueous phases were combined, adjusted to pH 2 with concentrated hydrochloric acid and washed three times with 500 ml of methylene chloride. Then, the combined organic phases were washed once with 10% strength hydrochloric acid. The organic phase was dried over sodium sulfate. Finally, the solvent was distilled off in vacuo. Yield: 120 g (87% of theory) of the desired product of purity >99% according to GC. The mixture was cooled by slowly stirring to room temperature overnight the mixture was heated to 80° C the phases were separated the aqueous phase was back-extracted twice with 500 ml of methyl tert.-butyl ether The combined methyl tert.-butyl ether phases were washed once with 800 ml of 10% strength aqueous sodium hydroxide solution and once with 400 ml of water washed three times with 500 ml of methylene chloride Then, the combined organic phases were washed once with 10% strength hydrochloric acid The organic phase was dried over sodium sulfate Finally, the solvent was distilled off in vacuo

反応条件: temp:2.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 640.5 g (4.6 mol) of difluorobenzonitrile were dissolved in 3.5 l of methanol and then cooled to 0-5° C. 828.8 g of 30% strength sodium methoxide solution were added dropwise in this temperature range, and the reaction mixture was stirred at room temperature overnight. Then the reaction mixture was added to 20 l of water and the precipitate was filtered off with suction and washed twice with water and twice with heptane. The solid was dried in vacuo at 50° C. Yield: 740 g (99% of theory) of a white solid with a purity of >95% according to GC. the precipitate was filtered off with suction washed twice with water and twice with heptane The solid was dried in vacuo at 50° C

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 709.5 mg (9.45 mmol) of acetohydroxamic acid are initially charged in 8 ml of anhydrous dimethylformamide, and 1.06 g (9.45 mmol) of potassium tert-butoxide are added at room temperature. After 40 minutes of stirring, 1 g (6.62 mmol) of 2-fluoro-6-methoxybenzonitrile is added. The mixture is heated at 60° C. for 16 hours. 20 ml of saturated sodium chloride solution are then added to the reaction mixture. The precipitated crystals are filtered off with suction and washed with water. The precipitated crystals are filtered off with suction washed with water

反応条件: temp:190.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 151 g (1 mol) of 2-fluoro-6-methoxybenzonitrile and 346.5 g (3 mol) of pyridinium hydrochloride were introduced into a 2 l flask and then slowly heated to 190° C. under a protective gas atmosphere and then stirred at this temperature for 5 h. The mixture was cooled by slowly stirring to room temperature overnight. Then 1000 ml of water were added, and the mixture was heated to 80° C. After adding 1000 ml of methyl tert.-butyl ether, the phases were separated and the aqueous phase was back-extracted twice with 500 ml of methyl tert.-butyl ether. The combined methyl tert.-butyl ether phases were washed once with 800 ml of 10% strength aqueous sodium hydroxide solution and once with 400 ml of water. The two aqueous phases were combined, adjusted to pH 2 with concentrated hydrochloric acid and washed three times with 500 ml of methylene chloride. Then, the combined organic phases were washed once with 10% strength hydrochloric acid. The organic phase was dried over sodium sulfate. Finally, the solvent was distilled off in vacuo. Yield: 120 g (87% of theory) of the desired product of purity >99% according to GC. The mixture was cooled by slowly stirring to room temperature overnight the mixture was heated to 80° C the phases were separated the aqueous phase was back-extracted twice with 500 ml of methyl tert.-butyl ether The combined methyl tert.-butyl ether phases were washed once with 800 ml of 10% strength aqueous sodium hydroxide solution and once with 400 ml of water washed three times with 500 ml of methylene chloride Then, the combined organic phases were washed once with 10% strength hydrochloric acid The organic phase was dried over sodium sulfate Finally, the solvent was distilled off in vacuo

反応条件: temp:2.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 640.5 g (4.6 mol) of difluorobenzonitrile were dissolved in 3.5 l of methanol and then cooled to 0-5° C. 828.8 g of 30% strength sodium methoxide solution were added dropwise in this temperature range, and the reaction mixture was stirred at room temperature overnight. Then the reaction mixture was added to 20 l of water and the precipitate was filtered off with suction and washed twice with water and twice with heptane. The solid was dried in vacuo at 50° C. Yield: 740 g (99% of theory) of a white solid with a purity of >95% according to GC. the precipitate was filtered off with suction washed twice with water and twice with heptane The solid was dried in vacuo at 50° C

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 709.5 mg (9.45 mmol) of acetohydroxamic acid are initially charged in 8 ml of anhydrous dimethylformamide, and 1.06 g (9.45 mmol) of potassium tert-butoxide are added at room temperature. After 40 minutes of stirring, 1 g (6.62 mmol) of 2-fluoro-6-methoxybenzonitrile is added. The mixture is heated at 60° C. for 16 hours. 20 ml of saturated sodium chloride solution are then added to the reaction mixture. The precipitated crystals are filtered off with suction and washed with water. The precipitated crystals are filtered off with suction washed with water

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

実験手順: 7.8 g of 2-methoxy-6-fluorobenzonitrile and 18.0 g of pyridine hydrochloride were heated for 5 hours at 195° C. under dry nitrogen. After cooling, the batch was partitioned between 50 ml of water and 50 ml of tert-butyl methyl ether, and the organic phase was subsequently extracted with 40 ml of 2N NaOH. The alkali extract was brought to pH 5 and subsequently extracted twice with in each case 40 ml of tert-butyl methyl ether. After the solvent had been evaporated, 4.7 g of the desired product were obtained as an oil (HPLC: 93%). After cooling the batch was partitioned between 50 ml of water and 50 ml of tert-butyl methyl ether the organic phase was subsequently extracted with 40 ml of 2N NaOH The alkali extract subsequently extracted twice with in each case 40 ml of tert-butyl methyl ether After the solvent had been evaporated

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

実験手順: 7.8 g of 2-methoxy-6-fluorobenzonitrile and 18.0 g of pyridine hydrochloride were heated for 5 hours at 195° C. under dry nitrogen. After cooling, the batch was partitioned between 50 ml of water and 50 ml of tert-butyl methyl ether, and the organic phase was subsequently extracted with 40 ml of 2N NaOH. The alkali extract was brought to pH 5 and subsequently extracted twice with in each case 40 ml of tert-butyl methyl ether. After the solvent had been evaporated, 4.7 g of the desired product were obtained as an oil (HPLC: 93%). After cooling the batch was partitioned between 50 ml of water and 50 ml of tert-butyl methyl ether the organic phase was subsequently extracted with 40 ml of 2N NaOH The alkali extract subsequently extracted twice with in each case 40 ml of tert-butyl methyl ether After the solvent had been evaporated