2-(4-broMo-2,6-difluorophenyl)acetonitrile

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

Procedure: A solution of 2-(4-bromo-2,6-difluorophenyl)acetonitrile (0.5 g, 2.155 mmol) in H2SO4 (3 mL, 56.3 mmol) and H2O (3 mL, 167 mmol) was stirred at 60° C. for 16 h. After LCMS analysis showed the starting material had disappeared, the mixture was dissolved in H2O (20 mL) and extracted by EA (2×30 mL). The organic layer was dried over Na2SO4, filtered and concentrated. The crude material was purified by silica column chromatography (PE/EA=3/1 to 1/1) to yield 2-(4-bromo-2,6-difluorophenyl)acetic acid (0.3 g, 0.718 mmol, 33.3% yield): 1H NMR (400 MHz, CD3OD) δ 7.13-7.05 (m, 2H), 3.71 (s, 2H). extracted by EA (2×30 mL) The organic layer was dried over Na2SO4 filtered concentrated The crude material was purified by silica column chromatography (PE/EA=3/1 to 1/1)

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 5-bromo-2-(bromomethyl)-1,3-difluorobenzene (1.6 g, 5.60 mmol) in DMF (20 mL) was added KCN (0.401 g, 6.16 mmol). The resulting mixture was stirred at 25° C. for 16 h. The mixture was dissolved in H2O (50 mL) and extracted by EA (50 mL). The organic layer was dried over Na2SO4, filtered and concentrated. The crude material was purified by silica column chromatography (PE/EA=3/1) to yield a white solid of 2-(4-bromo-2,6-difluorophenyl)acetonitrile (1.1 g, 2.57 mmol, 45.9% yield): 1H NMR (400 MHz, CD3OD) δ 7.39-7.36 (m, 2H), 3.89 (s, 2H). extracted by EA (50 mL) The organic layer was dried over Na2SO4 filtered concentrated The crude material was purified by silica column chromatography (PE/EA=3/1)

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 5-bromo-2-(bromomethyl)-1,3-difluorobenzene (1.6 g, 5.60 mmol) in DMF (20 mL) was added KCN (0.401 g, 6.16 mmol). The resulting mixture was stirred at 25° C. for 16 h. The mixture was dissolved in H2O (50 mL) and extracted by EA (50 mL). The organic layer was dried over Na2SO4, filtered and concentrated. The crude material was purified by silica column chromatography (PE/EA=3/1) to yield a white solid of 2-(4-bromo-2,6-difluorophenyl)acetonitrile (1.1 g, 2.57 mmol, 45.9% yield): 1H NMR (400 MHz, CD3OD) δ 7.39-7.36 (m, 2H), 3.89 (s, 2H). extracted by EA (50 mL) The organic layer was dried over Na2SO4 filtered concentrated The crude material was purified by silica column chromatography (PE/EA=3/1)

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

Procedure: A solution of 2-(4-bromo-2,6-difluorophenyl)acetonitrile (0.5 g, 2.155 mmol) in H2SO4 (3 mL, 56.3 mmol) and H2O (3 mL, 167 mmol) was stirred at 60° C. for 16 h. After LCMS analysis showed the starting material had disappeared, the mixture was dissolved in H2O (20 mL) and extracted by EA (2×30 mL). The organic layer was dried over Na2SO4, filtered and concentrated. The crude material was purified by silica column chromatography (PE/EA=3/1 to 1/1) to yield 2-(4-bromo-2,6-difluorophenyl)acetic acid (0.3 g, 0.718 mmol, 33.3% yield): 1H NMR (400 MHz, CD3OD) δ 7.13-7.05 (m, 2H), 3.71 (s, 2H). extracted by EA (2×30 mL) The organic layer was dried over Na2SO4 filtered concentrated The crude material was purified by silica column chromatography (PE/EA=3/1 to 1/1)

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 5-bromo-2-(bromomethyl)-1,3-difluorobenzene (1.6 g, 5.60 mmol) in DMF (20 mL) was added KCN (0.401 g, 6.16 mmol). The resulting mixture was stirred at 25° C. for 16 h. The mixture was dissolved in H2O (50 mL) and extracted by EA (50 mL). The organic layer was dried over Na2SO4, filtered and concentrated. The crude material was purified by silica column chromatography (PE/EA=3/1) to yield a white solid of 2-(4-bromo-2,6-difluorophenyl)acetonitrile (1.1 g, 2.57 mmol, 45.9% yield): 1H NMR (400 MHz, CD3OD) δ 7.39-7.36 (m, 2H), 3.89 (s, 2H). extracted by EA (50 mL) The organic layer was dried over Na2SO4 filtered concentrated The crude material was purified by silica column chromatography (PE/EA=3/1)

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 5-bromo-2-(bromomethyl)-1,3-difluorobenzene (1.6 g, 5.60 mmol) in DMF (20 mL) was added KCN (0.401 g, 6.16 mmol). The resulting mixture was stirred at 25° C. for 16 h. The mixture was dissolved in H2O (50 mL) and extracted by EA (50 mL). The organic layer was dried over Na2SO4, filtered and concentrated. The crude material was purified by silica column chromatography (PE/EA=3/1) to yield a white solid of 2-(4-bromo-2,6-difluorophenyl)acetonitrile (1.1 g, 2.57 mmol, 45.9% yield): 1H NMR (400 MHz, CD3OD) δ 7.39-7.36 (m, 2H), 3.89 (s, 2H). extracted by EA (50 mL) The organic layer was dried over Na2SO4 filtered concentrated The crude material was purified by silica column chromatography (PE/EA=3/1)

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 5-bromo-2-(bromomethyl)-1,3-difluorobenzene (1.6 g, 5.60 mmol) in DMF (20 mL) was added KCN (0.401 g, 6.16 mmol). The resulting mixture was stirred at 25° C. for 16 h. The mixture was dissolved in H2O (50 mL) and extracted by EA (50 mL). The organic layer was dried over Na2SO4, filtered and concentrated. The crude material was purified by silica column chromatography (PE/EA=3/1) to yield a white solid of 2-(4-bromo-2,6-difluorophenyl)acetonitrile (1.1 g, 2.57 mmol, 45.9% yield): 1H NMR (400 MHz, CD3OD) δ 7.39-7.36 (m, 2H), 3.89 (s, 2H). extracted by EA (50 mL) The organic layer was dried over Na2SO4 filtered concentrated The crude material was purified by silica column chromatography (PE/EA=3/1)

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 5-bromo-2-(bromomethyl)-1,3-difluorobenzene (1.6 g, 5.60 mmol) in DMF (20 mL) was added KCN (0.401 g, 6.16 mmol). The resulting mixture was stirred at 25° C. for 16 h. The mixture was dissolved in H2O (50 mL) and extracted by EA (50 mL). The organic layer was dried over Na2SO4, filtered and concentrated. The crude material was purified by silica column chromatography (PE/EA=3/1) to yield a white solid of 2-(4-bromo-2,6-difluorophenyl)acetonitrile (1.1 g, 2.57 mmol, 45.9% yield): 1H NMR (400 MHz, CD3OD) δ 7.39-7.36 (m, 2H), 3.89 (s, 2H). extracted by EA (50 mL) The organic layer was dried over Na2SO4 filtered concentrated The crude material was purified by silica column chromatography (PE/EA=3/1)

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

Procedure: To a mixture of potassium cyanide (0.55 g, 8.4 mmol) in dimethyl sulfoxide (10 mL) at 23° C. was slowly added 5-bromo-2-(bromomethyl)-1,3-difluorobenzene (2 g, 7.0 mmol), and the reaction mixture was stirred for 3 h. The reaction mixture was poured into saturated aqueous sodium chloride (100 mL) and was extracted with ether (3×100 mL). The combined organic layers were washed with saturated aq sodium chloride (3×50 mL), dried over anhydrous sodium sulfate, and concentrated to dryness. Purification of the residue by flash chromatography (0-100% ethyl acetate/hexanes) afforded the title product (0.84 g, 52%). 1H NMR (400 MHz, DMSO-d6) δ ppm 4.04 (s, 2 H) 7.60-7.62 (m, 1 H) 7.62-7.65 (m, 1 H). was extracted with ether (3×100 mL) The combined organic layers were washed with saturated aq sodium chloride (3×50 mL) dried over anhydrous sodium sulfate concentrated to dryness Purification of the residue by flash chromatography (0-100% ethyl acetate/hexanes)

Conditions: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of sulfuric acid (0.96 mL, 18.1 mmol) in acetic acid (20 mL) was slowly added 2-(4-bromo-2,6-difluorophenyl)acetonitrile (0.84 g, 3.6 mmol) portion-wise while stirring, and the reaction mixture was then stirred for 1 h at 100° C. After cooling to 5° C., the mixture was carefully adjusted to pH 9 with 28-30% aq ammonium hydroxide and then was extracted with chloroform (3×40 mL). The combined organic layers were dried over anhydrous sodium sulfate and concentrated in vacuo. Purification of the residue by flash chromatography (0-100% ethyl acetate/hexanes) provided the title product (0.71 g, 78%). MS(ES+) m/e 250 [M+H]+; 1H NMR (400 MHz, CD2Cl2) δ ppm 3.60 (s, 2 H) 5.54 (br. s., 2 H) 7.10-7.21 (m, 2 H). the reaction mixture was then stirred for 1 h at 100° C was extracted with chloroform (3×40 mL) The combined organic layers were dried over anhydrous sodium sulfate concentrated in vacuo Purification of the residue by flash chromatography (0-100% ethyl acetate/hexanes)

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

Procedure: A solution of 2-(4-bromo-2,6-difluorophenyl)acetonitrile (0.5 g, 2.155 mmol) in H2SO4 (3 mL, 56.3 mmol) and H2O (3 mL, 167 mmol) was stirred at 60° C. for 16 h. After LCMS analysis showed the starting material had disappeared, the mixture was dissolved in H2O (20 mL) and extracted by EA (2×30 mL). The organic layer was dried over Na2SO4, filtered and concentrated. The crude material was purified by silica column chromatography (PE/EA=3/1 to 1/1) to yield 2-(4-bromo-2,6-difluorophenyl)acetic acid (0.3 g, 0.718 mmol, 33.3% yield): 1H NMR (400 MHz, CD3OD) δ 7.13-7.05 (m, 2H), 3.71 (s, 2H). extracted by EA (2×30 mL) The organic layer was dried over Na2SO4 filtered concentrated The crude material was purified by silica column chromatography (PE/EA=3/1 to 1/1)

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 5-bromo-2-(bromomethyl)-1,3-difluorobenzene (1.6 g, 5.60 mmol) in DMF (20 mL) was added KCN (0.401 g, 6.16 mmol). The resulting mixture was stirred at 25° C. for 16 h. The mixture was dissolved in H2O (50 mL) and extracted by EA (50 mL). The organic layer was dried over Na2SO4, filtered and concentrated. The crude material was purified by silica column chromatography (PE/EA=3/1) to yield a white solid of 2-(4-bromo-2,6-difluorophenyl)acetonitrile (1.1 g, 2.57 mmol, 45.9% yield): 1H NMR (400 MHz, CD3OD) δ 7.39-7.36 (m, 2H), 3.89 (s, 2H). extracted by EA (50 mL) The organic layer was dried over Na2SO4 filtered concentrated The crude material was purified by silica column chromatography (PE/EA=3/1)