4-bromo-2-fluoro-1-phenylbenzene

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: To a stirred suspension of anhydrous aluminum chloride (3.35 g, 0.0251 mol) in dichloromethane (30 mL) at 5° C. under nitrogen was added dropwise a solution of 4-bromo-2-fluoro-biphenyl (2.512 g, 0.0100 mol) in dichloromethane (17 mL) followed by a solution of 3-carbomethoxypropionyl chloride (1.34 mL, 0.0109 mol) in dichloromethane (16 mL), and the mixture stirred. After 2 hours at 5° C., the mixture was allowed to warm to room temperature and stirred for 20 hours. The reaction was recooled to 5° C. and quenched by the dropwise addition of water (60 mL). The organic layer was washed with water, saturated sodium bicarbonate, brine, and dried (Na2SO4). The organics were rotary evaporated, and the residue was purified by chromatography on silica gel, eluting with chloroform to give 3.15 g of 4-(4′-bromo-2′-fluoro-biphenyl-4-yl)-4-oxo-butyric acid, methyl ester as a pale yellow solid; mp 94-95° C. stirred for 20 hours was recooled to 5° C. quenched by the dropwise addition of water (60 mL) The organic layer was washed with water, saturated sodium bicarbonate, brine dried (Na2SO4) the residue was purified by chromatography on silica gel eluting with chloroform

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 150 g of 4-bromo-2-fluorobiphenyl, 89.6 g of isopropenyl acetate, 258 ml of tributyltin butoxide and 4.7 g of a palladium chloride-tri(o-phenyl)phosphine complex were added to 300 ml of toluene and the mixture was stirred under heating at 80° C. for 2 hours under a nitrogen atmosphere. The reaction solution was left to cool to room temperature. Then, 1 l of ethyl acetate and 500 ml of a saturated potassium fluoride aqueous solution were added thereto, and the mixture was vigorously stirred. Insoluble matters were separated by filtration, and then the organic layer was collected by separation. The obtained organic layer was post-treated by a conventional method. The product was treated with hexane to obtain 106 g (yield: 78%) of 1-(2-fluoro-4-biphenylyl)-2-propanone. The reaction solution was left to cool to room temperature the mixture was vigorously stirred Insoluble matters were separated by filtration the organic layer was collected by separation The obtained organic layer was post-treated by a conventional method The product was treated with hexane

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

実験手順: In a reactor were placed 113 g of anhydrous aluminum chloride and 600 1 of methylene chloride, to which was added 113 g of acetylchloride under stirring at 0° C. or less. Subsequently, a solution of 100 g of 2-fluoro-4-bromobiphenyl in 400 ml methylene chloride was added dropwise, stirred and reacted together for 7 hours while increasing the temperature up to room temperature. After adding the reaction solution to ice/dilute hydrochloric acid, the methylene chloride layer was washed sequentially with water, aqueous sodium hydrogencarbonate solution, and water, followed by dehydration over Glauber's salt and distillation of the solvent. The remaining fraction was recrystallized with acetone to obtain 2-fluoro-4-bromo-4'-acetylbiphenyl. In a reactor were placed stirred reacted together for 7 hours After adding the reaction solution to ice/dilute hydrochloric acid the methylene chloride layer was washed sequentially with water, aqueous sodium hydrogencarbonate solution, and water followed by dehydration over Glauber's salt and distillation of the solvent The remaining fraction was recrystallized with acetone

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

実験手順: Solutions of 375 ml (325 g, 2.8 moles) of isoamyl nitrite, and of 378 grams (2.0 moles) of crude 4-bromo-2-fluoroaniline in 250 ml benzene are added separately and simultaneously dropwise over about 20 hours to 3500 ml of benzene vigorously stirred under a nitrogen atmosphere, and kept in a water bath at 65° C. The mixture is kept overnight at 65° C., then cooled, washed twice with 250 ml of water and evaporated. The dark oily residue is dissolved in 750 ml methanol and 450 ml concentrated hydrochloric acid, and treated with 138 grams (2.1 moles) of granular zinc, added in small portions over about 6 hours. In order to complete this "reductive upgrading", the solution is treated with 54 grams (1.0 mole) of fine iron filings over 0.5 hours. Within one hour the color of the mixture is visibly lighter. The solution is diluted with one liter of water and one liter of Skellysolve B hexanes, and the liquids are decanted from the remaining metals. The aqueous phase is extracted twice with one liter of Skellysolve B hexanes and the one liter of water, one liter of 1 N NaOH, and one liter of water. The solution is then passed through anhydrous sodium sulfate and evaporated to provide 389 grams of 4-bromo-2-fluoro-biphenyl. kept in a water bath at 65° C cooled washed twice with 250 ml of water evaporated The dark oily residue is dissolved in 750 ml methanol added in small portions over about 6 hours Within one hour the color of the mixture is visibly lighter the liquids are decanted from the remaining metals The aqueous phase is extracted twice with one liter of Skellysolve B hexanes evaporated

反応条件: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 96 grams (0.50 mole) of crude 4-bromo-2-fluoroaniline and 60.0 grams (1.0 mole) of glacial acetic acid in 100 ml of benzene is added dropwise over 7 hours to a mixture of 69.0 grams (1.0 mole) of sodium nitrite, 69 ml water, and 700 ml of benzene kept at 65° C. The mixture is then allowed to stir at 65° C. overnight (12 hours) under a nitrogen atmosphere. The cooled mixture is washed twice with 400 ml of 1 N hydrochloric acid, then heated under reflux overnight (13 hours) with 20 grams (0.36 mole) of iron powder, 250 ml of methanol, and 150 ml (1.8 moles) of concentrated hydrochloric acid. The resultant solution is cooled and the benzene layer is washed with 490 ml of water, and evaporated at 40° C./40 mm Hg. The resultant dark oil is distilled at 10 mm Hg pressure to obtain 64.6 grams (51.5%) of 4-bromo-2-fluorobiphenyl as the entire distillate of boiling point mostly ~132~141° C./8 mm. The product crystalizes on seeding. kept at 65° C The cooled mixture is washed twice with 400 ml of 1 N hydrochloric acid heated the benzene layer is washed with 490 ml of water evaporated at 40° C./40 mm Hg The resultant dark oil is distilled at 10 mm Hg pressure