2-(4-bromo-3-fluorophenyl)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:; See reaction.notes.procedure_details.

Procedure: (4-bromo-3-fluorophenyl)acetonitrile (40 g, 0.18 mol) was dissolved in 120 mL methanol, and 65 mL concentrated sulfuric acid were added. After heating at reflux overnight, the reaction mixture was cooled, and poured into 600 mL water, and the product was extracted with CH2Cl2. The combined extracts were washed with 10% sodium carbonate solution, dried, and concentrated to afford methyl (4-bromo-3-fluorophenyl)acetate. After heating at reflux overnight the reaction mixture was cooled the product was extracted with CH2Cl2 The combined extracts were washed with 10% sodium carbonate solution dried concentrated

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

Procedure: Powered sodium cyanide (12.0 g, 0.24 mol) was dissolved in a 20 mL of water, and was added a solution of 1-bromo-4-(bromomethyl)-2-fluorobenzene (60 g, 0.22 mol) in 30 mL of ethanol. After heating at reflux for 4 h, the reaction mixture was cooled to room temperature and filtered. The filtrate was concentrated, and the residue was diluted with CH2Cl2, filtered, and concentrated to afford (4-bromo-3-fluorophenyl)acetonitrile, which was used without further purification. After heating at reflux for 4 h filtered The filtrate was concentrated the residue was diluted with CH2Cl2 filtered concentrated

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

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

Procedure: To a solution of 1-bromo-4-(bromomethyl)-2-fluorobenzene (1 g, 3.73 mmol) in EtOH (30 mL) was added KCN (0.243 g, 3.73 mmol). The resulting mixture was stirred at 60° C. After 3 h, LCMS analysis showed the starting material had disappeared. The solvent was removed in vacuo. The residue was dissolved in EA (80 mL) was washed with H2O (30 mL) and brine (30 mL). The organic layer was dried and concentrated to give the crude product, which was purified by silica column chromatography (PE/EA=10/1) to yield a white solid of 2-(4-bromo-3-fluorophenyl)acetonitrile (0.78 g, 2.96 mmol, 79.0% yield): 1H NMR (400 MHz, CD3OD) δ 7.63 (t, J=7.8 Hz, 1H), 7.24 (d, J=9.2 Hz, 1H), 7.12 (d, J=9.6 Hz, 1H), 3.92 (s, 2H); ES-LCMS m/z 214.0 (M+H). The solvent was removed in vacuo The residue was dissolved in EA (80 mL) was washed with H2O (30 mL) and brine (30 mL) The organic layer was dried concentrated to give the crude product, which was purified by silica column chromatography (PE/EA=10/1)

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

Procedure: A solution of 4-bromo-3-fluorophenylacetonitrile (5 g, 23 mmoles) in toluene (20 ml) is added with 35 mmoles of 1,2-dibromoethane, a 50% NaOH aqueous solution (20 ml) and tetrabutylammonium bromide (1.6 g, 5 mmoles). The mixture is kept under stirring at room temperature for 5-12 hours, then diluted with water and extracted with ethyl acetate. The organic phase is washed with 1N HCl, then with brine, finally dried and concentrated under vacuum to give a brown solid, which is subjected to chromatography on a silica gel column (200 g), eluting with hexane-ethyl ether 1-1, to afford the product in the solid form. extracted with ethyl acetate The organic phase is washed with 1N HCl with brine, finally dried concentrated under vacuum to give a brown solid, which eluting with hexane-ethyl ether 1-1 to afford the product in the solid form

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

Procedure: A solution of 4-bromo-3-fluorobenzyl bromide (12.2 g, 0.03 moles) in ethanol (100 ml) is added with NaCN (2 g, 0.04 moles) and refluxed for 2 hours. The mixture is concentrated under vacuum; the resulting residue is taken up with water, then extracted with ethyl acetate. The organic phase is washed with brine, dried over sodium sulfate and concentrated under vacuum to give a dark oil (10 g), which is subjected to chromatography on a silica gel column (150 g), eluting with hexane:ethyl ether 7:3, to afford the product in the solid form. refluxed for 2 hours The mixture is concentrated under vacuum extracted with ethyl acetate The organic phase is washed with brine dried over sodium sulfate concentrated under vacuum

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

Procedure: A solution of 4-bromo-3-fluorobenzyl bromide (12.2 g, 0.03 moles) in ethanol (100 ml) is added with NaCN (2 g, 0.04 moles) and refluxed for 2 hours. The mixture is concentrated under vacuum; the resulting residue is taken up with water, then extracted with ethyl acetate. The organic phase is washed with brine, dried over sodium sulfate and concentrated under vacuum to give a dark oil (10 g), which is subjected to chromatography on a silica gel column (150 g), eluting with hexane:ethyl ether 7:3, to afford the product in the solid form. refluxed for 2 hours The mixture is concentrated under vacuum extracted with ethyl acetate The organic phase is washed with brine dried over sodium sulfate concentrated under vacuum

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

Procedure: To a solution of 1-bromo-4-(bromomethyl)-2-fluorobenzene (1 g, 3.73 mmol) in ethanol (30 mL) was added KCN (0.243 g, 3.73 mmol). The resulting mixture was stirred at 60° C. After 3 h, LCMS analysis showed the starting material had disappeared. The solvent was removed in vacuo. The residue was dissolved in EA (80 mL) was washed with H2O (30 mL) and brine (30 mL). The organic layer was dried and concentrated to give the crude product, which was purified by silica column chromatography (PE/EA=10/1) to yield a white solid of 2-(4-bromo-3-fluorophenyl)acetonitrile (0.78 g, 2.96 mmol, 79.0% yield): 1H NMR (400 MHz, CD3OD) δ 7.63 (t, J=7.8 Hz, 1H), 7.24 (d, J=9.2 Hz, 1H), 7.12 (d, J=9.6 Hz, 1H), 3.92 (s, 2H); ES-LCMS m/z 214.0 (M+H). The solvent was removed in vacuo The residue was dissolved in EA (80 mL) was washed with H2O (30 mL) and brine (30 mL) The organic layer was dried concentrated to give the crude product, which was purified by silica column chromatography (PE/EA=10/1)

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

Procedure: To a solution of 1-bromo-4-(bromomethyl)-2-fluorobenzene (1 g, 3.73 mmol) in ethanol (30 mL) was added KCN (0.243 g, 3.73 mmol). The resulting mixture was stirred at 60° C. After 3 h, LCMS analysis showed the starting material had disappeared. The solvent was removed in vacuo. The residue was dissolved in EA (80 mL) was washed with H2O (30 mL) and brine (30 mL). The organic layer was dried and concentrated to give the crude product, which was purified by silica column chromatography (PE/EA=10/1) to yield a white solid of 2-(4-bromo-3-fluorophenyl)acetonitrile (0.78 g, 2.96 mmol, 79.0% yield): 1H NMR (400 MHz, CD3OD) δ 7.63 (t, J=7.8 Hz, 1H), 7.24 (d, J=9.2 Hz, 1H), 7.12 (d, J=9.6 Hz, 1H), 3.92 (s, 2H); ES-LCMS m/z 214.0 (M+H). The solvent was removed in vacuo The residue was dissolved in EA (80 mL) was washed with H2O (30 mL) and brine (30 mL) The organic layer was dried concentrated to give the crude product, which was purified by silica column chromatography (PE/EA=10/1)

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

Procedure: (4-bromo-3-fluorophenyl)acetonitrile (40 g, 0.18 mol) was dissolved in 120 mL methanol, and 65 mL concentrated sulfuric acid were added. After heating at reflux overnight, the reaction mixture was cooled, and poured into 600 mL water, and the product was extracted with CH2Cl2. The combined extracts were washed with 10% sodium carbonate solution, dried, and concentrated to afford methyl (4-bromo-3-fluorophenyl)acetate. After heating at reflux overnight the reaction mixture was cooled the product was extracted with CH2Cl2 The combined extracts were washed with 10% sodium carbonate solution dried concentrated