2-(2-bromo-5-methoxyphenyl)acetonitrile

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To (2-bromo-5-methoxy-phenyl)-acetonitrile (2.6 g, 11.5 mmol) in CH2Cl2 (20 mL) at 0° C. under N2 was added boron tribromide (1M in CH2Cl2; 25.4 mL, 25.4 mmol). The mixture was stirred for 15 minutes at 0° C., and at mom temperature overnight. After a work-up with H2O and CH2Cl2, the crude material was purified by silica gel chromatography to give the desired product as a white solid (1.5 g). at mom temperature overnight After a work-up with H2O and CH2Cl2, the crude material was purified by silica gel chromatography

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To (2-bromo-5-methoxy-phenyl)-acetonitrile (2.6 g, 11.5 mmol) in CH2Cl2 (20 mL) at 0° C. under N2 was added boron tribromide (1M in CH2Cl2; 25.4 mL, 25.4 mmol). The mixture was stirred for 15 minutes at 0° C., and at mom temperature overnight. After a work-up with H2O and CH2Cl2, the crude material was purified by silica gel chromatography to give the desired product as a white solid (1.5 g). at mom temperature overnight After a work-up with H2O and CH2Cl2, the crude material was purified by silica gel chromatography

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-Bromo-5-methoxybenzyl bromide (2 g, 7.1 mmol) and sodium cyanide (0.526 g, 10.7 mmol) were combined in DMSO (20 mL) and heated to 90° C. for 3 hours. Once no starting material was seen by analytical tlc, the mixture was worked-up with H2O and EtOAc to give the desired product as a colorless oil.

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

実験手順: To the THF solution (1000 ml) of 2-bromo-5-methoxy-benzoic acid methyl ester (20 g, 81.6 mmol), the THF suspension (50 ml) of LAH (4.07 g, 102 mmol) was added under ice cooling. The mixture was stirred for 30 min under ice cooling. The reaction solution was partitioned between saturated aqueous solution of Na2SO4 and ethyl acetate. The organic layer was washed with saturated brine and concentrated under reduced pressure. The resulting residues were dissolved in DCM (200 ml), and added with TEA (12.51 ml, 89.76 mmol) and MsCl (6.63 ml, 85.68 mmol) under ice cooling, followed by stirring overnight at room temperature. The reaction mixture was diluted with DCM, and washed in order with 10% aqueous solution of citric acid, saturated aqueous solution of NaHCO3 and saturated brine. The residues obtained after concentration under reduced pressure were dissolved in DMF (100 ml), and added with the DMF (500 ml) solution of NaCN (40 g, 81.6 mmol) under ice cooling. After stirring for 2 hrs under ice cooling, the reaction mixture was extracted with ether, washed with saturated brine and dried over magnesium sulfate. The residues obtained after concentration under reduced pressure were purified by silica gel column (hexane:ethyl acetate=10:1) to obtain the title compound (12.1 g, 67%). The reaction solution was partitioned between saturated aqueous solution of Na2SO4 and ethyl acetate The organic layer was washed with saturated brine concentrated under reduced pressure The resulting residues were dissolved in DCM (200 ml) by stirring overnight at room temperature washed in order with 10% aqueous solution of citric acid, saturated aqueous solution of NaHCO3 and saturated brine The residues obtained after concentration under reduced pressure were dissolved in DMF (100 ml) After stirring for 2 hrs under ice cooling the reaction mixture was extracted with ether washed with saturated brine dried over magnesium sulfate The residues obtained after concentration under reduced pressure were purified by silica gel column (hexane:ethyl acetate=10:1)

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 the THF solution (1000 ml) of 2-bromo-5-methoxy-benzoic acid methyl ester (20 g, 81.6 mmol), the THF suspension (50 ml) of LAH (4.07 g, 102 mmol) was added under ice cooling. The mixture was stirred for 30 min under ice cooling. The reaction solution was partitioned between saturated aqueous solution of Na2SO4 and ethyl acetate. The organic layer was washed with saturated brine and concentrated under reduced pressure. The resulting residues were dissolved in DCM (200 ml), and added with TEA (12.51 ml, 89.76 mmol) and MsCl (6.63 ml, 85.68 mmol) under ice cooling, followed by stirring overnight at room temperature. The reaction mixture was diluted with DCM, and washed in order with 10% aqueous solution of citric acid, saturated aqueous solution of NaHCO3 and saturated brine. The residues obtained after concentration under reduced pressure were dissolved in DMF (100 ml), and added with the DMF (500 ml) solution of NaCN (40 g, 81.6 mmol) under ice cooling. After stirring for 2 hrs under ice cooling, the reaction mixture was extracted with ether, washed with saturated brine and dried over magnesium sulfate. The residues obtained after concentration under reduced pressure were purified by silica gel column (hexane:ethyl acetate=10:1) to obtain the title compound (12.1 g, 67%). The reaction solution was partitioned between saturated aqueous solution of Na2SO4 and ethyl acetate The organic layer was washed with saturated brine concentrated under reduced pressure The resulting residues were dissolved in DCM (200 ml) by stirring overnight at room temperature washed in order with 10% aqueous solution of citric acid, saturated aqueous solution of NaHCO3 and saturated brine The residues obtained after concentration under reduced pressure were dissolved in DMF (100 ml) After stirring for 2 hrs under ice cooling the reaction mixture was extracted with ether washed with saturated brine dried over magnesium sulfate The residues obtained after concentration under reduced pressure were purified by silica gel column (hexane:ethyl acetate=10:1)

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

実験手順: To the THF solution (1000 ml) of 2-bromo-5-methoxy-benzoic acid methyl ester (20 g, 81.6 mmol), the THF suspension (50 ml) of LAH (4.07 g, 102 mmol) was added under ice cooling. The mixture was stirred for 30 min under ice cooling. The reaction solution was partitioned between saturated aqueous solution of Na2SO4 and ethyl acetate. The organic layer was washed with saturated brine and concentrated under reduced pressure. The resulting residues were dissolved in DCM (200 ml), and added with TEA (12.51 ml, 89.76 mmol) and MsCl (6.63 ml, 85.68 mmol) under ice cooling, followed by stirring overnight at room temperature. The reaction mixture was diluted with DCM, and washed in order with 10% aqueous solution of citric acid, saturated aqueous solution of NaHCO3 and saturated brine. The residues obtained after concentration under reduced pressure were dissolved in DMF (100 ml), and added with the DMF (500 ml) solution of NaCN (40 g, 81.6 mmol) under ice cooling. After stirring for 2 hrs under ice cooling, the reaction mixture was extracted with ether, washed with saturated brine and dried over magnesium sulfate. The residues obtained after concentration under reduced pressure were purified by silica gel column (hexane:ethyl acetate=10:1) to obtain the title compound (12.1 g, 67%). The reaction solution was partitioned between saturated aqueous solution of Na2SO4 and ethyl acetate The organic layer was washed with saturated brine concentrated under reduced pressure The resulting residues were dissolved in DCM (200 ml) by stirring overnight at room temperature washed in order with 10% aqueous solution of citric acid, saturated aqueous solution of NaHCO3 and saturated brine The residues obtained after concentration under reduced pressure were dissolved in DMF (100 ml) After stirring for 2 hrs under ice cooling the reaction mixture was extracted with ether washed with saturated brine dried over magnesium sulfate The residues obtained after concentration under reduced pressure were purified by silica gel column (hexane:ethyl acetate=10:1)

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

実験手順: To the THF solution (1000 ml) of 2-bromo-5-methoxy-benzoic acid methyl ester (20 g, 81.6 mmol), the THF suspension (50 ml) of LAH (4.07 g, 102 mmol) was added under ice cooling. The mixture was stirred for 30 min under ice cooling. The reaction solution was partitioned between saturated aqueous solution of Na2SO4 and ethyl acetate. The organic layer was washed with saturated brine and concentrated under reduced pressure. The resulting residues were dissolved in DCM (200 ml), and added with TEA (12.51 ml, 89.76 mmol) and MsCl (6.63 ml, 85.68 mmol) under ice cooling, followed by stirring overnight at room temperature. The reaction mixture was diluted with DCM, and washed in order with 10% aqueous solution of citric acid, saturated aqueous solution of NaHCO3 and saturated brine. The residues obtained after concentration under reduced pressure were dissolved in DMF (100 ml), and added with the DMF (500 ml) solution of NaCN (40 g, 81.6 mmol) under ice cooling. After stirring for 2 hrs under ice cooling, the reaction mixture was extracted with ether, washed with saturated brine and dried over magnesium sulfate. The residues obtained after concentration under reduced pressure were purified by silica gel column (hexane:ethyl acetate=10:1) to obtain the title compound (12.1 g, 67%). The reaction solution was partitioned between saturated aqueous solution of Na2SO4 and ethyl acetate The organic layer was washed with saturated brine concentrated under reduced pressure The resulting residues were dissolved in DCM (200 ml) by stirring overnight at room temperature washed in order with 10% aqueous solution of citric acid, saturated aqueous solution of NaHCO3 and saturated brine The residues obtained after concentration under reduced pressure were dissolved in DMF (100 ml) After stirring for 2 hrs under ice cooling the reaction mixture was extracted with ether washed with saturated brine dried over magnesium sulfate The residues obtained after concentration under reduced pressure were purified by silica gel column (hexane:ethyl acetate=10:1)

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 NH4Cl (3.58 g, 66.37 mmol) in dry toluene (100 mL) was added trimethyl aluminium (2M in toluene, 33.18 mL, 66.37 mmol) at 5° C., then the mixture was warmed to room temperature and stirred for 2 h. A solution of (2-bromo-5-methoxy-phenyl)-acetonitrile (136) (5 g, 22.12 mmol) in toluene (25 mL) was added to the above reaction mixture and the mixture was then stirred for 14 h at 80° C. After completion of the reaction, it was quenched with a suspension of silica gel in chloroform and the reaction mixture was stirred for half an hour at room temperature and filtered through a sintered funnel, the silica gel was washed with methanol and the combined filtrate was concentrated under reduced pressure to get 2-(2-bromo-5-methoxyphenyl)-acetamidine hydrochloride salt as a crude product (137) (4 g, 74.37%) a as white solid. the mixture was then stirred for 14 h at 80° C After completion of the reaction, it was quenched with a suspension of silica gel in chloroform the reaction mixture was stirred for half an hour at room temperature filtered through a sintered funnel the silica gel was washed with methanol the combined filtrate was concentrated under reduced pressure

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

実験手順: 5-Methoxy-2-bromophenylacetonitrile (52.8 g, 0.23 mol) is dissolved in ethanol (250 mL) and stirred at room temperature. Sodium hydroxide (9.3 g, 0.47 mol) is dissolved in water (150 mL) and added to the solution of the nitrile. The mixture is heated to reflux temperature for 12 hours and then cooled to room temperature. Most of the ethanol is removed using a rotary evaporator and the residual aqueous solution adjusted to pH 4 with 3 N HCl. The solid which forms is isolated by filtration and washed with water. Air drying gives 5-methoxy-2-bromophenylacetic acid. The mixture is heated to reflux temperature for 12 hours cooled to room temperature Most of the ethanol is removed a rotary evaporator The solid which forms is isolated by filtration washed with water Air drying

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

実験手順: 5-Methoxy-2-bromobenzyl bromide (72.8 g, 0.26 mol) is dissolved in EtOH (280 mL) and stirred at room temperature. Sodium cyanide (38.2 g, 0.78 mol) is dissolved in water and added to the solution of the bromide. The reaction mixture is heated to reflux temperature for 3 hours and then cooled to room temperature. Most of the ethanol is removed by rotary evaporator. A solid forms which is isolated by filtration and washed with water (500 mL). The crude material is purified using flash chromatography (CH2Cl2/hexanes, 1:1) to give 5-methoxy-2-bromophenylacetonitrile (53 g). The reaction mixture is heated to reflux temperature for 3 hours cooled to room temperature Most of the ethanol is removed by rotary evaporator A solid forms which is isolated by filtration washed with water (500 mL) The crude material is purified