2-bromo-5-iodobenzonitrile

Conditions: temp:-40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 2-bromo-5-iodobenzonitrile (1457 mg, 4.730 mmol) in tetrahydrofuran (10 mL) at −40° C. was added isopropyl magnesium chloride.lithium chloride (1.3M in THF, 4.4 mL, 5.7 mmol) dropwise. The mixture was stirred at −40° C. for 10 minutes, and was then treated with cyclobutanone (0.4 mL, 5.2 mmol) dropwise at −40° C. The reaction mixture was warmed to room temperature and stirred at that temperature for 16 hours. The reaction mixture was poured into water (10 mL) and extracted with ethyl acetate (3×20 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo to give the title compound which was used directly in the next step without further purification. The reaction mixture was warmed to room temperature stirred at that temperature for 16 hours extracted with ethyl acetate (3×20 mL) The combined organic layers were dried over sodium sulfate filtered concentrated in vacuo

Conditions: temp:-40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 2-bromo-5-iodobenzonitrile (1457 mg, 4.730 mmol) in tetrahydrofuran (10 mL) at −40° C. was added isopropyl magnesium chloride.lithium chloride (1.3 M in THF, 4.4 mL, 5.7 mmol) dropwise. The mixture was stirred at −40° C. for 10 minutes, and was then treated with cyclobutanone (0.4 mL, 5.2 mmol) dropwise at −40° C. The reaction mixture was warmed to room temperature and stirred at that temperature for 16 hours. The reaction mixture was poured into water (10 mL) and extracted with ethyl acetate (3×20 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo to give the title compound which was used directly in the next step without further purification. The reaction mixture was warmed to room temperature stirred at that temperature for 16 hours extracted with ethyl acetate (3×20 mL) The combined organic layers were dried over sodium sulfate filtered concentrated in vacuo

Conditions: temp:-40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 2-bromo-5-iodobenzonitrile (1457 mg, 4.730 mmol) in tetrahydrofuran (10 mL) at −40° C. was added isopropyl magnesium chloride.lithium chloride (1.3 M in THF, 4.4 mL, 5.7 mmol) dropwise. The mixture was stirred at −40° C. for 10 minutes, and was then treated with cyclobutanone (0.4 mL, 5.2 mmol) dropwise at −40° C. The reaction mixture was warmed to room temperature and stirred at that temperature for 16 hours. The reaction mixture was poured into water (10 mL) and extracted with ethyl acetate (3×20 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo to give the title compound which was used directly in the next step without further purification. The reaction mixture was warmed to room temperature stirred at that temperature for 16 hours extracted with ethyl acetate (3×20 mL) The combined organic layers were dried over sodium sulfate filtered concentrated in vacuo

Conditions: temp:-40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 2-bromo-5-iodobenzonitrile (1457 mg, 4.730 mmol) in tetrahydrofuran (10 mL) at −40° C. was added isopropyl magnesium chloride.lithium chloride (1.3M in THF, 4.4 mL, 5.7 mmol) dropwise. The mixture was stirred at −40° C. for 10 minutes, and was then treated with cyclobutanone (0.4 mL, 5.2 mmol) dropwise at −40° C. The reaction mixture was warmed to room temperature and stirred at that temperature for 16 hours. The reaction mixture was poured into water (10 mL) and extracted with ethyl acetate (3×20 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo to give the title compound which was used directly in the next step without further purification. The reaction mixture was warmed to room temperature stirred at that temperature for 16 hours extracted with ethyl acetate (3×20 mL) The combined organic layers were dried over sodium sulfate filtered concentrated in vacuo

Conditions: temp:-40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 2-bromo-5-iodobenzonitrile (1457 mg, 4.730 mmol) in tetrahydrofuran (10 mL) at −40° C. was added isopropyl magnesium chloride.lithium chloride (1.3M in THF, 4.4 mL, 5.7 mmol) dropwise. The mixture was stirred at −40° C. for 10 minutes, and was then treated with cyclobutanone (0.4 mL, 5.2 mmol) dropwise at −40° C. The reaction mixture was warmed to room temperature and stirred at that temperature for 16 hours. The reaction mixture was poured into water (10 mL) and extracted with ethyl acetate (3×20 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo to give the title compound which was used directly in the next step without further purification. The reaction mixture was warmed to room temperature stirred at that temperature for 16 hours extracted with ethyl acetate (3×20 mL) The combined organic layers were dried over sodium sulfate filtered concentrated in vacuo

Conditions: temp:-8.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A round bottom flask was charged with the 2-bromo-5-iodobenzonitrile (2.00 g, 6.49 mmol) and THF (9 mL). Solution cooled down to −8° C. (ice/brine bath). Turbo Grignard 1.3M in THF (5.50 mL, 7.14 mmol) is then added in one portion and the reaction stirred for 15 minutes at −8° C. Butyraldehyde (0.698 μL, 7.79 mmol) is then charged in another flask and the preformed anion is added over the aldehyde/THF (4 mL) via canula and then, reaction allowed to warmed at room temperature overnight under magnetic stirring. Ammonium chloride (sat. aq.) added to the mixture. Extracted 3× with Ethyl Acetate. Combined organic layers washed with water (1×), with brine (1×), dried over sodium sulfate, filtered and concentrated to afford the crude material. Purification by silica gel flash chromatography (Ethyl Acetate/Heptane) provide the title compound as a yellow oil (1.33 g, 80.6%). 1H NMR (400 MHz, DMSO-d6) δ 0.83 (t, J=7.41 Hz, 3 H) 1.18-1.34 (m, 2 H) 1.46-1.57 (m, 2 H) 4.52-4.58 (m, 1 H) 5.37 (d, J=4.88 Hz, 1 H) 7.56 (dd, J=8.58, 1.95 Hz, 1 H) 7.79 (d, J=8.39 Hz, 1 H) 7.81 (d, J=2.15 Hz, 1 H); MS (M): 255. reaction allowed to warmed at room temperature overnight under magnetic stirring Extracted 3× with Ethyl Acetate Combined organic layers washed with water (1×), with brine (1×) dried over sodium sulfate filtered concentrated to afford the crude material Purification by silica gel flash chromatography (Ethyl Acetate/Heptane)

Conditions: temp:-8.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A round bottom flask was charged with the 2-bromo-5-iodobenzonitrile (2.00 g, 6.49 mmol) and THF (9 mL). Solution cooled down to −8° C. (ice/brine bath). Turbo Grignard 1.3M in THF (5.50 mL, 7.14 mmol) is then added in one portion and the reaction stirred for 15 minutes at −8° C. Butyraldehyde (0.698 μL, 7.79 mmol) is then charged in another flask and the preformed anion is added over the aldehyde/THF (4 mL) via canula and then, reaction allowed to warmed at room temperature overnight under magnetic stirring. Ammonium chloride (sat. aq.) added to the mixture. Extracted 3× with Ethyl Acetate. Combined organic layers washed with water (1×), with brine (1×), dried over sodium sulfate, filtered and concentrated to afford the crude material. Purification by silica gel flash chromatography (Ethyl Acetate/Heptane) provide the title compound as a yellow oil (1.33 g, 80.6%). 1H NMR (400 MHz, DMSO-d6) δ 0.83 (t, J=7.41 Hz, 3H) 1.18-1.34 (m, 2H) 1.46-1.57 (m, 2H) 4.52-4.58 (m, 1H) 5.37 (d, J=4.88 Hz, 1H) 7.56 (dd, J=8.58, 1.95 Hz, 1H) 7.79 (d, J=8.39 Hz, 1H) 7.81 (d, J=2.15 Hz, 1H); MS (M): 255. reaction allowed to warmed at room temperature overnight under magnetic stirring Extracted 3× with Ethyl Acetate Combined organic layers washed with water (1×), with brine (1×) dried over sodium sulfate filtered concentrated to afford the crude material Purification by silica gel flash chromatography (Ethyl Acetate/Heptane)

Conditions: temp:-8.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A round bottom flask was charged with the 2-bromo-5-iodobenzonitrile (2.00 g, 6.49 mmol) and THF (9 mL). Solution cooled down to −8° C. (ice/brine bath). Turbo Grignard 1.3M in THF (5.50 mL, 7.14 mmol) is then added in one portion and the reaction stirred for 15 minutes at −8° C. Butyraldehyde (0.698 μL, 7.79 mmol) is then charged in another flask and the preformed anion is added over the aldehyde/THF (4 mL) via canula and then, reaction allowed to warmed at room temperature overnight under magnetic stirring. Ammonium chloride (sat. aq.) added to the mixture. Extracted 3× with Ethyl Acetate. Combined organic layers washed with water (1×), with brine (1×), dried over sodium sulfate, filtered and concentrated to afford the crude material. Purification by silica gel flash chromatography (Ethyl Acetate/Heptane) provide the title compound as a yellow oil (1.33 g, 80.6%). 1H NMR (400 MHz, DMSO-d6) δ 0.83 (t, J=7.41 Hz, 3H) 1.18-1.34 (m, 2H) 1.46-1.57 (m, 2H) 4.52-4.58 (m, 1H) 5.37 (d, J=4.88 Hz, 1H) 7.56 (dd, J=8.58, 1.95 Hz, 1H) 7.79 (d, J=8.39 Hz, 1H) 7.81 (d, J=2.15 Hz, 1H); MS (M): 255. reaction allowed to warmed at room temperature overnight under magnetic stirring Extracted 3× with Ethyl Acetate Combined organic layers washed with water (1×), with brine (1×) dried over sodium sulfate filtered concentrated to afford the crude material Purification by silica gel flash chromatography (Ethyl Acetate/Heptane)

Conditions: temp:-40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 2-bromo-5-iodobenzonitrile (1457 mg, 4.730 mmol) in tetrahydrofuran (10 mL) at −40° C. was added isopropyl magnesium chloride.lithium chloride (1.3 M in THF, 4.4 mL, 5.7 mmol) dropwise. The mixture was stirred at −40° C. for 10 minutes, and was then treated with cyclobutanone (0.4 mL, 5.2 mmol) dropwise at −40° C. The reaction mixture was warmed to room temperature and stirred at that temperature for 16 hours. The reaction mixture was poured into water (10 mL) and extracted with ethyl acetate (3×20 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo to give the title compound which was used directly in the next step without further purification. The reaction mixture was warmed to room temperature stirred at that temperature for 16 hours extracted with ethyl acetate (3×20 mL) The combined organic layers were dried over sodium sulfate filtered concentrated in vacuo

Conditions: temp:-40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 2-bromo-5-iodobenzonitrile (1457 mg, 4.730 mmol) in tetrahydrofuran (10 mL) at −40° C. was added isopropyl magnesium chloride.lithium chloride (1.3M in THF, 4.4 mL, 5.7 mmol) dropwise. The mixture was stirred at −40° C. for 10 minutes, and was then treated with cyclobutanone (0.4 mL, 5.2 mmol) dropwise at −40° C. The reaction mixture was warmed to room temperature and stirred at that temperature for 16 hours. The reaction mixture was poured into water (10 mL) and extracted with ethyl acetate (3×20 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo to give the title compound which was used directly in the next step without further purification. The reaction mixture was warmed to room temperature stirred at that temperature for 16 hours extracted with ethyl acetate (3×20 mL) The combined organic layers were dried over sodium sulfate filtered concentrated in vacuo