2-(4-bromophenyl)acetonitrile

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred suspension of sodium hydride (60% susp. in oil, 12.24 g, 255 mmol) in anhydrous DMSO (240 mL) is added dropwise 2-(4-bromophenyl)acetonitrile (20.0 g, 102 mmol) dissolved in anhydrous DMSO (40 mL). After 45 min, the reaction mixture is cooled to 0° C. and 1,3-dibromopropane (30.9 g, 15.5 mL, 153 mmol) dissolved in anhydrous DMSO (40 mL) is added slowly to maintain the temperature below 45° C. The reaction mixture is stirred overnight at room temperature and poured in cold water (1.2 L). The product is extracted with CH2Cl2 (6×100 mL), dried on MgSO4, filtered and concentrated under reduced pressure. The product is purified by flash chromatography eluting with hexane:EtOAc (100% to 95:5) to provide the expected product 1-(4-bromophenyl)cyclobutanecarbonitrile (9.9 g, 41%) as a yellowish oil. 1H NMR (300 MHz, CHLOROFORM-D): δ 7.57-7.49 (2H, m), 7.33-7.24 (2H, m), 2.89-2.77 (2H, m), 2.66-2.34 (3H, m), 2.15-1.99 (1H, m). is added slowly to maintain the temperature below 45° C The product is extracted with CH2Cl2 (6×100 mL) dried on MgSO4 filtered concentrated under reduced pressure The product is purified by flash chromatography eluting with hexane

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 50.0 g (225.0 mmol) of 4-bromophenylacetonitrile and 1.8 g (12.8 mmol) of potassium carbonate in 387 mL of dimethyl carbonate was heated to 180° C. in a sealed vessel for 16 hours. The solution was then cooled, diluted with 200 ml of ethyl acetate and washed once with 100 ml water, once with 100 ml of 10% aqueous sodium bisulfate and once with 100 ml brine. The organic portion was dried (MgSO4), filtered and concentrated in vacuo. The residue was distilled under vacuum through a short path distillation apparatus to afford 40.3 g (85%) of the title compound. The solution was then cooled washed once with 100 ml water, once with 100 ml of 10% aqueous sodium bisulfate and once with 100 ml brine The organic portion was dried (MgSO4) filtered concentrated in vacuo The residue was distilled under vacuum through a short path distillation apparatus

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Bromophenylacetonitrile (5.0 g, 25.5 mmol), hydroxylamine hydrochloride (3.9 g, 56.1 mmol), and sodium bicarbonate (5.1 g, 61.2 mmol) were dissolved in MeOH (250 mL, 6.2 mol) and water (40 mL, 2 mol). The mixture was heated at reflux overnight, cooled, and then concentrated to 50 mL. The residue was dissolved in DCM, washed with water and saturated aqueous NaCl, dried over MgSO4, filtered and concentrated to yield 2-(4-bromophenyl)-N-hydroxyacetamidine (5.0 g). The mixture was heated at reflux overnight cooled concentrated to 50 mL The residue was dissolved in DCM washed with water and saturated aqueous NaCl dried over MgSO4 filtered concentrated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Bromophenylacetonitrile (5.0 g, 25.5 mmol), hydroxylamine hydrochloride (3.9 g, 56.1 mmol), and sodium bicarbonate (5.1 g, 61.2 mmol) were dissolved in MeOH (250 mL, 6.2 mol) and water (40 mL, 2 mol). The mixture was heated at reflux overnight, cooled, and then concentrated to 50 mL. The residue was dissolved in DCM, washed with water and saturated aqueous NaCl, dried over MgSO4, filtered and concentrated to yield 2-(4-bromophenyl)-N-hydroxyacetamidine (5.0 g). The mixture was heated at reflux overnight cooled concentrated to 50 mL The residue was dissolved in DCM washed with water and saturated aqueous NaCl dried over MgSO4 filtered concentrated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of sodium hydride (60% dispersion in oil, 50 g, 1.25 m) in dry N,N-dimethylformamide (400 ml under nitrogen was added with stirring a solution of 4-bromophenylacetonitrile in N,N-dimethylformamide (400 ml) keeping the temperature between 30° and 40° C. A solution of iodomethane (213 g, 1.50 m) in N,N-dimethylformamide was then added gradually keeping the temperatue between 35° C. and the mixture then stirred at ambient temperature overnight. With ice cooling 2N aqueous hydrochloric acid (800 ml) was gradually added and then the mixture was diluted with water (1200 ml). The product was extracted with ether and the extract washed with water, saturated sodium bicarbonate, aqueous sodium sulphite, water again and finally brine. After drying and concentration on vacuo an orange oil was obtained which was distilled in vacuo to give the title compound as a colourless liquid (98.05 g, 87.5%) b.pt. 98°-100°/0.4 mm. was added the temperature between 30° and 40° C between 35° C. The product was extracted with ether the extract washed with water, saturated sodium bicarbonate, aqueous sodium sulphite, water again After drying concentration on vacuo an orange oil was obtained which was distilled in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of sodium hydride (60% dispersion in oil, 50 g, 1.25 m) in dry N,N-dimethylformamide (400 ml under nitrogen was added with stirring a solution of 4-bromophenylacetonitrile in N,N-dimethylformamide (400 ml) keeping the temperature between 30° and 40° C. A solution of iodomethane (213 g, 1.50 m) in N,N-dimethylformamide was then added gradually keeping the temperatue between 35° C. and the mixture then stirred at ambient temperature overnight. With ice cooling 2N aqueous hydrochloric acid (800 ml) was gradually added and then the mixture was diluted with water (1200 ml). The product was extracted with ether and the extract washed with water, saturated sodium bicarbonate, aqueous sodium sulphite, water again and finally brine. After drying and concentration on vacuo an orange oil was obtained which was distilled in vacuo to give the title compound as a colourless liquid (98.05 g, 87.5%) b.pt. 98°-100°/0.4 mm. was added the temperature between 30° and 40° C between 35° C. The product was extracted with ether the extract washed with water, saturated sodium bicarbonate, aqueous sodium sulphite, water again After drying concentration on vacuo an orange oil was obtained which was distilled in vacuo