3-bromo-2-fluorophenol

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: 117 g of potassium carbonate and 55.6 g of bromohexane are added to a solution of 53.6 g of 3-bromo-2-fluorophenol in 650 ml of acetone, and the mixture is refluxed for 8 hours. The mixture is filtered, evaporated to ⅓ of the original volume and poured into 600 ml of water. The pH is adjusted to 1 using hydrochloric acid, and the mixture is extracted three times with 150 ml of tert-butyl methyl ether each time. The combined organic phases are concentrated under reduced pressure, and the residue is subjected to vacuum distillation (103° C.; 1 mbar), giving 67 g of 6-bromo-2-hexyloxyfluorobenzene as a colorless oil. 1H-NMR (CDCl3): 6.9-7.1 (m; 3H); 4.0 (t; 2H), 0.9-1.8 (m, 11H), 19F-NMR (CDCl3): −128 ppm. A solution of 67.3 g of 6-bromo-2-hexyloxyfluorobenzene, 24.7 g of 2-methyl-3-butyn-2-ol [115-19-5], 0.7 g of bis(triphenylphosphine)palladium(II) chloride and 0.7 g of copper iodide in 340 ml of triethylamine is refluxed for 5 hours. The mixture is then poured into 1.5 of ice-water, the pH is adjusted to 1 using hydrochloric acid, and the mixture is extracted three-times with 200 ml of tert-butyl methyl ether each time. The combined organic phases are dried under reduced pressure. The crude 4-(2-fluoro-3-hexyloxyphenyl)2methyl-3-butyn-1-ol is refluxed for 3 hours in 1000 ml of toluene together with three mole-equivalents of sodium hydroxide. The mixture is filtered and washed with dilute hydrochloric acid, the solvent is removed by distillation, and the residue is distilled (90° C.; 0.5 mbar), giving 34 g of 1-(2-fluoro-3-hexyloxyphenyl)ethyne. the mixture is refluxed for 8 hours The mixture is filtered evaporated poured into 600 ml of water the mixture is extracted three times with 150 ml of tert-butyl methyl ether each time The combined organic phases are concentrated under reduced pressure the residue is subjected to vacuum distillation (103° C.; 1 mbar)

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

実験手順: 117 g of potassium carbonate and 55.6 g of bromohexane are added to a solution of 53.6 g of 3-bromo-2-fluorophenol in 650 ml of acetone, and the mixture is refluxed for 8 hours. The mixture is filtered, evaporated to ⅓ of the original volume and poured into 600 ml of water. The pH is adjusted to 1 using hydrochloric acid, and the mixture is extracted three times with 150 ml of tert-butyl methyl ether each time. The combined organic phases are concentrated under reduced pressure, and the residue is subjected to vacuum distillation (103° C.; 1 mbar), giving 67 g of 6-bromo-2-hexyloxyfluorobenzene as a colorless oil. 1H-NMR (CDCl3): 6.9-7.1 (m; 3H); 4.0 (t; 2H), 0.9-1.8 (m, 11H), 19F-NMR (CDCl3): −128 ppm. A solution of 67.3 g of 6-bromo-2-hexyloxyfluorobenzene, 24.7 g of 2-methyl-3-butyn-2-ol [115-19-5], 0.7 g of bis(triphenylphosphine)palladium(II) chloride and 0.7 g of copper iodide in 340 ml of triethylamine is refluxed for 5 hours. The mixture is then poured into 1.5 of ice-water, the pH is adjusted to 1 using hydrochloric acid, and the mixture is extracted three-times with 200 ml of tert-butyl methyl ether each time. The combined organic phases are dried under reduced pressure. The crude 4-(2-fluoro-3-hexyloxyphenyl)2methyl-3-butyn-1-ol is refluxed for 3 hours in 1000 ml of toluene together with three mole-equivalents of sodium hydroxide. The mixture is filtered and washed with dilute hydrochloric acid, the solvent is removed by distillation, and the residue is distilled (90° C.; 0.5 mbar), giving 34 g of 1-(2-fluoro-3-hexyloxyphenyl)ethyne. the mixture is refluxed for 8 hours The mixture is filtered evaporated poured into 600 ml of water the mixture is extracted three times with 150 ml of tert-butyl methyl ether each time The combined organic phases are concentrated under reduced pressure the residue is subjected to vacuum distillation (103° C.; 1 mbar)

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

実験手順: 125 ml of a 35% strength aqueous solution of hydrogen peroxide are added dropwise at room temperature to the crude 2-bromo-1-fluorophenylboronic acid (80 g) dissolved in 300 ml of tert-butyl methyl ether; during this addition, the temperature rises to 55° C. When the addition is complete, the mixture is refluxed for a further 2 hours. After the mixture has been cooled, 100 ml of water are added, and the organic phase is extracted by shaking twice with saturated sodium sulfite solution. After the solvent has been removed by distillation under reduced pressure, vacuum distillation (90° C.; 4 mbar) gives 54 g of 3-bromo-2-fluorophenol as an oil which soon crystallizes. 1H-NMR (CDCl3): 6.9-7.1 (m; 3H); 5.1 (br; 1H), 19F-NMR (CDCl3): −135 ppm. during this addition rises to 55° C When the addition the mixture is refluxed for a further 2 hours After the mixture has been cooled the organic phase is extracted After the solvent has been removed by distillation under reduced pressure, vacuum distillation (90° C.; 4 mbar)

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

実験手順: To a stirred mixture of 3-bromo-2-fluoro-phenol (19.5 g, 0.102 mol) and ethyl-2-butynoate (22.0 g, 0.196 mol) in tetrahydrofuran (100 mL) was added 1,8-diazabicyclo[5.4.0]undec-7-ene (15.6 g, 0.102 mol) slowly. After addition was complete the mixture was stirred at reflux for overnight. Upon completion of the reaction the tetrahydrofuran was removed in vacuo and the residue was diluted in diethyl ether and washed first with 1N aqueous hydrochloric acid, then 10% aqueous sodium hydroxide solution, a saturated sodium chloride solution and dried over magnesium sulfate. The mixture was filtered and evaporated, and the residue dried under high vacuum which afforded (E)-3-(3-bromo-2-fluoro-phenoxy)-but-2-enoic acid ethyl ester as a brown oil (21.5 g, 69%) and used without further purification. After addition at reflux for overnight was removed in vacuo the residue was diluted in diethyl ether washed first with 1N aqueous hydrochloric acid 10% aqueous sodium hydroxide solution, a saturated sodium chloride solution and dried over magnesium sulfate The mixture was filtered evaporated the residue dried under high vacuum which

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

実験手順: To a solution of 3-bromo-2-fluoro-phenylboronic acid (25.0 g, 0.114 mol) in tetrahydrofuran (250 mL) was added glacial acetic acid (150 mL). The resulting mixture was cooled to 0° C. before hydrogen peroxide (50% aqueous solution, 25 mL) was added. The resulting mixture was allowed to come to room temperature and stirred for 24 h. The mixture was evaporated and the residue was dissolved in ethyl acetate, washed with hydrochloric acid (0.5N), water and brine. The organic phase was dried, filtered and evaporated which afforded 3-bromo-2-fluoro-phenol (19.50 g, 89%) as a brown solid. was added to come to room temperature The mixture was evaporated the residue was dissolved in ethyl acetate washed with hydrochloric acid (0.5N), water and brine The organic phase was dried filtered evaporated which

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

実験手順: To a stirred mixture of 3-bromo-2-fluoro-phenol (19.5 g, 0.102 mol) and ethyl-2-butynoate (22.0 g, 0.196 mol) in tetrahydrofuran (100 mL) was added 1,8-diazabicyclo[5.4.0]undec-7-ene (15.6 g, 0.102 mol) slowly. After addition was complete the mixture was stirred at reflux for overnight. Upon completion of the reaction the tetrahydrofuran was removed in vacuo and the residue was diluted in diethyl ether and washed first with 1N aqueous hydrochloric acid, then 10% aqueous sodium hydroxide solution, a saturated sodium chloride solution and dried over magnesium sulfate. The mixture was filtered and evaporated, and the residue dried under high vacuum which afforded (E)-3-(3-bromo-2-fluoro-phenoxy)-but-2-enoic acid ethyl ester as a brown oil (21.5 g, 69%) and used without further purification. After addition at reflux for overnight was removed in vacuo the residue was diluted in diethyl ether washed first with 1N aqueous hydrochloric acid 10% aqueous sodium hydroxide solution, a saturated sodium chloride solution and dried over magnesium sulfate The mixture was filtered evaporated the residue dried under high vacuum which

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

実験手順: To a solution of 3-bromo-2-fluoro-phenylboronic acid (25.0 g, 0.114 mol) in tetrahydrofuran (250 mL) was added glacial acetic acid (150 mL). The resulting mixture was cooled to 0° C. before hydrogen peroxide (50% aqueous solution, 25 mL) was added. The resulting mixture was allowed to come to room temperature and stirred for 24 h. The mixture was evaporated and the residue was dissolved in ethyl acetate, washed with hydrochloric acid (0.5N), water and brine. The organic phase was dried, filtered and evaporated which afforded 3-bromo-2-fluoro-phenol (19.50 g, 89%) as a brown solid. was added to come to room temperature The mixture was evaporated the residue was dissolved in ethyl acetate washed with hydrochloric acid (0.5N), water and brine The organic phase was dried filtered evaporated which

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

実験手順: To a solution of 3-bromo-2-fluorophenol (1.8 g, 9.42 mmol) in acetone (25 ml) was added sodium carbonate (2.55 g, 20 mmol) and the mixture was stirred for 5 min. Benzylbromide (1.2 ml, 10.3 mmol) was added and the reaction mixture was heated at reflux for 20 h. Water (50 ml) and ethyl acetate (50 ml) was added and the phases were separated. The aqueous phase was extracted with ethyl acetate (2×50 ml) and the combined organic phases was dried (MgSO4) and evaporated under reduced pressure to give an oil. The residue was purified by flash column chromatography (isooctane/ethyl acetate, 5:1) to give the title compound (2.8 g). MS m/z (rel. intensity, 70 eV) 282 (M+, 2), 280 (M+, 2), 163 (2), 161 (2), 91 (bp). the reaction mixture was heated at reflux for 20 h the phases were separated The aqueous phase was extracted with ethyl acetate (2×50 ml) the combined organic phases was dried (MgSO4) evaporated under reduced pressure to give an oil The residue was purified by flash column chromatography (isooctane/ethyl acetate, 5:1)

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

実験手順: To a solution of 3-bromo-2-fluorophenol (1.8 g, 9.42 mmol) in acetone (25 ml) was added sodium carbonate (2.55 g, 20 mmol) and the mixture was stirred for 5 min. Benzylbromide (1.2 ml, 10.3 mmol) was added and the reaction mixture was heated at reflux for 20 h. Water (50 ml) and ethyl acetate (50 ml) was added and the phases were separated. The aqueous phase was extracted with ethyl acetate (2×50 ml) and the combined organic phases was dried (MgSO4) and evaporated under reduced pressure to give an oil. The residue was purified by flash column chromatography (isooctane/ethyl acetate, 5:1) to give the title compound (2.8 g). MS m/z (rel. intensity, 70 eV) 282 (M+, 2), 280 (M+, 2), 163 (2), 161 (2), 91 (bp). the reaction mixture was heated at reflux for 20 h the phases were separated The aqueous phase was extracted with ethyl acetate (2×50 ml) the combined organic phases was dried (MgSO4) evaporated under reduced pressure to give an oil The residue was purified by flash column chromatography (isooctane/ethyl acetate, 5:1)