1-(4-bromo-2,5-difluorophenyl)ethanone

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:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Anhydrous aluminum chloride was mixed (5 grams, 37.5 millimoles, 2.4 equivalents) with 1-bromo-2,5 difluorobenzene in a dry, round-bottom flask blanketed with nitrogen and fitted with a condenser. The mixture was heated to 60° C. and acetyl chloride (1.7 milliliters, 23.3 millimole, 1.5. equivalents) was added by syringe. The wet yellow solid changed then into a scarlet solution and was heated at 90° C. for 1 hour. The reaction mixture was poured onto 38 grams of ice, HCl was added (3 milliliters, 37% concentration) and the mixture was extracted with ether. The crude material was dried over magnesium sulfate and evaporated down. The crude material was purified by column chromatography or distilled. The product (1.2 grams, 31%) was obtained as a yellow oil. fitted with a condenser into a scarlet solution and was heated at 90° C. for 1 hour was added (3 milliliters, 37% concentration) the mixture was extracted with ether The crude material was dried over magnesium sulfate evaporated down The crude material was purified by column chromatography distilled

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

実験手順: Anhydrous aluminum chloride was mixed (5 grams, 37.5 millimoles, 2.4 equivalents) with 1-bromo-2,5 difluorobenzene in a dry, round-bottom flask blanketed with nitrogen and fitted with a condenser. The mixture was heated to 60° C. and acetyl chloride (1.7 milliliters, 23.3 millimole, 1.5. equivalents) was added by syringe. The wet yellow solid changed then into a scarlet solution and was heated at 90° C. for 1 hour. The reaction mixture was poured onto 38 grams of ice, HCl was added (3 milliliters, 37% concentration) and the mixture was extracted with ether. The crude material was dried over magnesium sulfate and evaporated down. The crude material was purified by column chromatography or distilled. The product (1.2 grams, 31%) was obtained as a yellow oil. fitted with a condenser into a scarlet solution and was heated at 90° C. for 1 hour was added (3 milliliters, 37% concentration) the mixture was extracted with ether The crude material was dried over magnesium sulfate evaporated down The crude material was purified by column chromatography distilled

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

実験手順: Anhydrous aluminum chloride was mixed (5 grams, 37.5 millimoles, 2.4 equivalents) with 1-bromo-2,5 difluorobenzene in a dry, round-bottom flask blanketed with nitrogen and fitted with a condenser. The mixture was heated to 60° C. and acetyl chloride (1.7 milliliters, 23.3 millimole, 1.5. equivalents) was added by syringe. The wet yellow solid changed then into a scarlet solution and was heated at 90° C. for 1 hour. The reaction mixture was poured onto 38 grams of ice, HCl was added (3 milliliters, 37% concentration) and the mixture was extracted with ether. The crude material was dried over magnesium sulfate and evaporated down. The crude material was purified by column chromatography or distilled. The product (1.2 grams, 31%) was obtained as a yellow oil. fitted with a condenser into a scarlet solution and was heated at 90° C. for 1 hour was added (3 milliliters, 37% concentration) the mixture was extracted with ether The crude material was dried over magnesium sulfate evaporated down The crude material was purified by column chromatography distilled

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

実験手順: Acetyl chloride (17 ml) is slowly dropped into a stirred mixture of 1-bromo-2,5-difluorobenzene (30 g) and aluminium trichloride (53 g) heated at 60° C. and kept under argon. The reaction mixture is then stirred 90 minutes at 95° C. The mixture is cooled at 40° C. and carefully poured into crushed ice (400 g) and concentrated hydrochloric acid (35 ml). The resulting mixture is stirred a few minutes and then extracted with ethyl ether (2×250 ml). The ethereal solution is washed to neutral with brine, dried over sodium sulfate and the solvent is evaporated. The distillation of the oily residue gives 4'-bromo-2 ',5'-difluoroacetophenone (21.2 g) b.p. (0.05 mm)=60° C. The mixture is cooled at 40° C. carefully poured The resulting mixture is stirred a few minutes extracted with ethyl ether (2×250 ml) The ethereal solution is washed to neutral with brine dried over sodium sulfate the solvent is evaporated The distillation of the oily residue

反応条件: temp:95.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred mixture of 20 g 2,5-difluorobromobenzene and 35,2 g aluminum chloride under nitrogen at 60° C. was added dropwise 11.2 ml acetyl chloride. The reaction mixture was stirred at 95° C. for 90 min. and then poured over 250 g ice followed by 17 ml concentrated hydrochloric acid. The aqueous mixture was extracted with ether, and the extracts washed with sodium chloride solution and concentrated. The residue (23.6 g) was distilled in vacuo to give 18.4 g (76%) 4-bromo-2,5-difluoroacetophenone, b.p. 65° C. (0.1 mm). The aqueous mixture was extracted with ether the extracts washed with sodium chloride solution concentrated The residue (23.6 g) was distilled in vacuo

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

実験手順: To a stirred mixture of 18 g 4-bromo-2,5-difluoroacetophenone and 233 ml diethyl carbonate cooled in an ice-bath was slowly added 6.4 g sodium hydride (60% in oil). The reaction mixture was heated at 80° C. for 90 min. and then added to 700 ml ice containing 25 ml acetic acid. The aqueous mixture was extracted with ether, and the ether extracts were washed with sodium chloride solution, dried (magnesium sulfate) and concentrated. The residue was distilled, collecting the material (15.33 g) boiling at 85°-135° C. (0.05 mm). The latter material was chromatographed on 185 g silica gel (Kieselgel 60) using 20% ether in hexane as eluant to give 6.69 g ethyl 4-bromo-2,5-difluorobenzoylacetate as the first product to be eluted. cooled in an ice-bath The aqueous mixture was extracted with ether the ether extracts were washed with sodium chloride solution dried (magnesium sulfate) concentrated The residue was distilled collecting the material (15.33 g) boiling at 85°-135° C. (0.05 mm) The latter material was chromatographed on 185 g silica gel (Kieselgel 60)

反応条件: temp:95.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred mixture of 20 g 2,5-difluorobromobenzene and 35.2 g aluminum chloride under nitrogen at 60° C. was added dropwise 11.2 ml acetyl chloride. The reaction mixture was stirred at 95° C. for 90 min. and then poured over 250 g ice followed by 17 ml concentrated hydrochloric acid. The aqueous mixture was extracted with ether, and the extracts washed with sodium chloride solution and concentrated. The residue (23.6 g) was distilled in vacuo to give 18.4 g (76%) 4-bromo-2,5-difluoroacetophenone, b.p. 65° C. (0.1 mm). The aqueous mixture was extracted with ether the extracts washed with sodium chloride solution concentrated The residue (23.6 g) was distilled in vacuo

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

実験手順: 1-(4-bromo-2,5-difluorophenyl)ethanone (500 mg, 1.042 mmol) was dissolved in ethanol (10 mL), then hydrazine hydrate (57.4 mg, 1.147 mmol) added and stirred at RT for 16 hr. A pale yellow solid was filtered off and the filtrate was concentrated under reduced pressure to obtain the crude title compound as a brown-yellow solid (249 mg, 54% yield); 1H NMR (500 MHz, CHLOROFORM-d)delta 2.13 (3H, d, J=2.99 Hz), 7.28 (1H, dd, J=9.85, 5.60 Hz), 7.34 (1H, dd, J=9.14, 6.62 Hz). A pale yellow solid was filtered off the filtrate was concentrated under reduced pressure

反応条件: temp:95.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred mixture of 2-bromo-1,4-difluorobenzene (3.24 g, 16.81 mmol) and aluminium chloride (5.82 g, 43.7 mmol) at 60° C. under nitrogen was added dropwise acetyl chloride (1.98 g, 25.28 mmol 1). The mixture was stirred at 95° C. for 1.5 hr and then poured into ice (50 mL). To the mixture was added HCl (3 mL) followed by extraction into ether (20 mL×2). The ether extracts were washed with brine (20 mL) and then concentrated under reduced pressure to obtain the desired crude product (brown oil) as mixture with starting material (55:45) (2.67 g, 33%); 1H NMR (250 MHz, CHLOROFORM-d) delta 2.64 (3H, d, J=5.18 Hz), 7.42 (1H, dd, J=9.44, 5.18 Hz), 7.65 (1H, dd, J=8.45, 6.17 Hz). followed by extraction into ether (20 mL×2) The ether extracts were washed with brine (20 mL) concentrated under reduced pressure

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

実験手順: Anhydrous aluminum chloride was mixed (5 grams, 37.5 millimoles, 2.4 equivalents) with 1-bromo-2,5 difluorobenzene in a dry, round-bottom flask blanketed with nitrogen and fitted with a condenser. The mixture was heated to 60° C. and acetyl chloride (1.7 milliliters, 23.3 millimole, 1.5. equivalents) was added by syringe. The wet yellow solid changed then into a scarlet solution and was heated at 90° C. for 1 hour. The reaction mixture was poured onto 38 grams of ice, HCl was added (3 milliliters, 37% concentration) and the mixture was extracted with ether. The crude material was dried over magnesium sulfate and evaporated down. The crude material was purified by column chromatography or distilled. The product (1.2 grams, 31%) was obtained as a yellow oil. fitted with a condenser into a scarlet solution and was heated at 90° C. for 1 hour was added (3 milliliters, 37% concentration) the mixture was extracted with ether The crude material was dried over magnesium sulfate evaporated down The crude material was purified by column chromatography distilled