2-(4-bromo-2-methoxyphenyl)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: To a stirring mixture of (4-bromo-2-methoxyphenyl)acetonitrile (904 mg, 4.00 mmol), 1,3-dibromo-propane (880 mg, 4.40 mmol) in dimethylformamide (10 mL) was added sodium hydride (352 mg, 8.80 mmol) at 0° C. After addition, the mixture was stirred at room temperature for 3 hours. The reaction mixture was quenched with water and extracted with dichloromethane (50 mL×3). The organic phases were combined, dried over sodium sulfate and concentrated in vacuo to give a brown solid. The solid was purification by combiflash chromatography (Petroleum ether/EtOAc=20:1 to 5:1) to give the title compound (370 mg, 34.8%) as a white solid. 1H NMR (400 MHz, CDCl3) δ 7.10 (dd, 1H), 7.02 (d, 1H), 7.00 (d, 1H), 3.87 (s, 3H), 2.78 (m, 2H), 2.50 (m, 3H), 1.95 (m, 1H) After addition The reaction mixture was quenched with water extracted with dichloromethane (50 mL×3) dried over sodium sulfate concentrated in vacuo to give a brown solid purification by combiflash chromatography (Petroleum ether/EtOAc=20:1 to 5:1)

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

Procedure: To a solution of potassium tert-butoxide (6.5 g, 0.058 mol) in 1,2-dimethoxyethane (150 mL) was added p-toluenesulfonylmethyl isocyanide (5.6 g, 0.029 mol) portionwise at −78° C. Then a solution of 4-bromo-2-methoxybenzaldehyde (6.3 g, 0.029 mol) in 1,2-dimethoxyethane was added dropwise and the reaction mixture was warmed to room temperature. The mixture was stirred at room temperature for 1 hour and methanol (150 mL) was added, then heated to reflux and stirred for 2 hours. Solvent was evaporated, and saturated ammonium chloride (100 mL) was added and extracted with ethyl acetate (100 mL×2). The organic layers were combined, dried over sodium sulfate and concentrated in vacuo to give a residue, which was purified by combiflash (Petroleum ether/EtOAc=10:1 to 5:1) to give the title compound (5.4 g, 82%) as a light yellow solid. heated to reflux stirred for 2 hours Solvent was evaporated saturated ammonium chloride (100 mL) was added extracted with ethyl acetate (100 mL×2) dried over sodium sulfate concentrated in vacuo to give a residue, which was purified by combiflash (Petroleum ether/EtOAc=10:1 to 5:1)

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

Procedure: To a stirring mixture of (4-bromo-2-methoxyphenyl)acetonitrile (904 mg, 4.00 mmol), 1,3-dibromo-propane (880 mg, 4.40 mmol) in dimethylformamide (10 mL) was added sodium hydride (352 mg, 8.80 mmol) at 0° C. After addition, the mixture was stirred at room temperature for 3 hours. The reaction mixture was quenched with water and extracted with dichloromethane (50 mL×3). The organic phases were combined, dried over sodium sulfate and concentrated in vacuo to give a brown solid. The solid was purification by combiflash chromatography (Petroleum ether/EtOAc=20:1 to 5:1) to give the title compound (370 mg, 34.8%) as a white solid. 1H NMR (400 MHz, CDCl3) δ 7.10 (dd, 1H), 7.02 (d, 1H), 7.00 (d, 1H), 3.87 (s, 3H), 2.78 (m, 2H), 2.50 (m, 3H), 1.95 (m, 1H) After addition The reaction mixture was quenched with water extracted with dichloromethane (50 mL×3) dried over sodium sulfate concentrated in vacuo to give a brown solid purification by combiflash chromatography (Petroleum ether/EtOAc=20:1 to 5:1)

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

Procedure: To a solution of potassium tert-butoxide (6.5 g, 0.058 mol) in 1,2-dimethoxyethane (150 mL) was added p-toluenesulfonylmethyl isocyanide (5.6 g, 0.029 mol) portionwise at −78° C. Then a solution of 4-bromo-2-methoxybenzaldehyde (6.3 g, 0.029 mol) in 1,2-dimethoxyethane was added dropwise and the reaction mixture was warmed to room temperature. The mixture was stirred at room temperature for 1 hour and methanol (150 mL) was added, then heated to reflux and stirred for 2 hours. Solvent was evaporated, and saturated ammonium chloride (100 mL) was added and extracted with ethyl acetate (100 mL×2). The organic layers were combined, dried over sodium sulfate and concentrated in vacuo to give a residue, which was purified by combiflash (Petroleum ether/EtOAc=10:1 to 5:1) to give the title compound (5.4 g, 82%) as a light yellow solid. 1H NMR (400 MHz, CDCl3) δ 7.25 (d, 1H), 7.12 (d, 1H), 7.03 (s, 1H), 3.87 (s, 3H), 3.63 (s, 2H) heated to reflux stirred for 2 hours Solvent was evaporated saturated ammonium chloride (100 mL) was added extracted with ethyl acetate (100 mL×2) dried over sodium sulfate concentrated in vacuo to give a residue, which was purified by combiflash (Petroleum ether/EtOAc=10:1 to 5:1)

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

Procedure: To a solution of potassium tert-butoxide (6.5 g, 0.058 mol) in 1,2-dimethoxyethane (150 mL) was added p-toluenesulfonylmethyl isocyanide (5.6 g, 0.029 mol) portionwise at −78° C. Then a solution of 4-bromo-2-methoxybenzaldehyde (6.3 g, 0.029 mol) in 1,2-dimethoxyethane was added dropwise and the reaction mixture was warmed to room temperature. The mixture was stirred at room temperature for 1 hour and methanol (150 mL) was added, then heated to reflux and stirred for 2 hours. Solvent was evaporated, and saturated ammonium chloride (100 mL) was added and extracted with ethyl acetate (100 mL×2). The organic layers were combined, dried over sodium sulfate and concentrated in vacuo to give a residue, which was purified by combiflash (Petroleum ether/EtOAc=10:1 to 5:1) to give the title compound (5.4 g, 82%) as a light yellow solid. 1H NMR (400 MHz, CDCl3) δ 7.25 (d, 1H), 7.12 (d, 1H), 7.03 (s, 1H), 3.87 (s, 3H), 3.63 (s, 2H) heated to reflux stirred for 2 hours Solvent was evaporated saturated ammonium chloride (100 mL) was added extracted with ethyl acetate (100 mL×2) dried over sodium sulfate concentrated in vacuo to give a residue, which was purified by combiflash (Petroleum ether/EtOAc=10:1 to 5:1)

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

Procedure: A solution of NaOH (5.72 g, 143 mmol) in water (29 mL) was added to a solution of (4-bromo-2-methoxy-phenyl)-acetonitrile (10.2 g, 45.1 mmol) in MeOH (100 mL). The reaction mixture was heated at reflux for 18 hours. The solvent was evaporated under reduced pressure and water was added. The aqueous mixture was washed with diethyl ether, and the aqueous layer was acidified by addition of aqueous HCl (2 M) to pH 1. The aqueous mixture was then extracted with EtOAc, and the combined organic extracts were washed with brine, dried over Na2SO4, filtered, and evaporated under reduced pressure to give 9.49 g (86% yield) of (4-bromo-2-methoxy-phenyl)-acetic acid. The reaction mixture was heated at reflux for 18 hours The solvent was evaporated under reduced pressure and water was added The aqueous mixture was washed with diethyl ether the aqueous layer was acidified by addition of aqueous HCl (2 M) to pH 1 The aqueous mixture was then extracted with EtOAc the combined organic extracts were washed with brine dried over Na2SO4 filtered evaporated under reduced pressure

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

Procedure: To a stirring mixture of (4-bromo-2-methoxyphenyl)acetonitrile (904 mg, 4.00 mmol), 1,3-dibromo-propane (880 mg, 4.40 mmol) in dimethylformamide (10 mL) was added sodium hydride (352 mg, 8.80 mmol) at 0° C. After addition, the mixture was stirred at room temperature for 3 hours. The reaction mixture was quenched with water and extracted with dichloromethane (50 mL×3). The organic phases were combined, dried over sodium sulfate and concentrated in vacuo to give a brown solid. The solid was purification by combiflash chromatography (Petroleum ether/EtOAc=20:1 to 5:1) to give the title compound (370 mg, 34.8%) as a white solid. 1H NMR (400 MHz, CDCl3) δ 7.10 (dd, 1H), 7.02 (d, 1H), 7.00 (d, 1H), 3.87 (s, 3H), 2.78 (m, 2H), 2.50 (m, 3H), 1.95 (m, 1H) After addition The reaction mixture was quenched with water extracted with dichloromethane (50 mL×3) dried over sodium sulfate concentrated in vacuo to give a brown solid purification by combiflash chromatography (Petroleum ether/EtOAc=20:1 to 5:1)

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

Procedure: To a stirring mixture of (4-bromo-2-methoxyphenyl)acetonitrile (904 mg, 4.00 mmol), 1,3-dibromo-propane (880 mg, 4.40 mmol) in dimethylformamide (10 mL) was added sodium hydride (352 mg, 8.80 mmol) at 0° C. After addition, the mixture was stirred at room temperature for 3 hours. The reaction mixture was quenched with water and extracted with dichloromethane (50 mL×3). The organic phases were combined, dried over sodium sulfate and concentrated in vacuo to give a brown solid. The solid was purification by combiflash chromatography (Petroleum ether/EtOAc=20:1 to 5:1) to give the title compound (370 mg, 34.8%) as a white solid. 1H NMR (400 MHz, CDCl3) δ 7.10 (dd, 1H), 7.02 (d, 1H), 7.00 (d, 1H), 3.87 (s, 3H), 2.78 (m, 2H), 2.50 (m, 3H), 1.95 (m, 1H) After addition The reaction mixture was quenched with water extracted with dichloromethane (50 mL×3) dried over sodium sulfate concentrated in vacuo to give a brown solid purification by combiflash chromatography (Petroleum ether/EtOAc=20:1 to 5:1)

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

Procedure: To a solution of potassium tert-butoxide (6.5 g, 0.058 mol) in 1,2-dimethoxyethane (150 mL) was added p-toluenesulfonylmethyl isocyanide (5.6 g, 0.029 mol) portionwise at −78° C. Then a solution of 4-bromo-2-methoxybenzaldehyde (6.3 g, 0.029 mol) in 1,2-dimethoxyethane was added dropwise and the reaction mixture was warmed to room temperature. The mixture was stirred at room temperature for 1 hour and methanol (150 mL) was added, then heated to reflux and stirred for 2 hours. Solvent was evaporated, and saturated ammonium chloride (100 mL) was added and extracted with ethyl acetate (100 mL×2). The organic layers were combined, dried over sodium sulfate and concentrated in vacuo to give a residue, which was purified by combiflash (Petroleum ether/EtOAc=10:1 to 5:1) to give the title compound (5.4 g, 82%) as a light yellow solid. heated to reflux stirred for 2 hours Solvent was evaporated saturated ammonium chloride (100 mL) was added extracted with ethyl acetate (100 mL×2) dried over sodium sulfate concentrated in vacuo to give a residue, which was purified by combiflash (Petroleum ether/EtOAc=10:1 to 5:1)

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

Procedure: To a solution of potassium tert-butoxide (6.5 g, 0.058 mol) in 1,2-dimethoxyethane (150 mL) was added p-toluenesulfonylmethyl isocyanide (5.6 g, 0.029 mol) portionwise at −78° C. Then a solution of 4-bromo-2-methoxybenzaldehyde (6.3 g, 0.029 mol) in 1,2-dimethoxyethane was added dropwise and the reaction mixture was warmed to room temperature. The mixture was stirred at room temperature for 1 hour and methanol (150 mL) was added, then heated to reflux and stirred for 2 hours. Solvent was evaporated, and saturated ammonium chloride (100 mL) was added and extracted with ethyl acetate (100 mL×2). The organic layers were combined, dried over sodium sulfate and concentrated in vacuo to give a residue, which was purified by combiflash (Petroleum ether/EtOAc=10:1 to 5:1) to give the title compound (5.4 g, 82%) as a light yellow solid. heated to reflux stirred for 2 hours Solvent was evaporated saturated ammonium chloride (100 mL) was added extracted with ethyl acetate (100 mL×2) dried over sodium sulfate concentrated in vacuo to give a residue, which was purified by combiflash (Petroleum ether/EtOAc=10:1 to 5:1)