4-bromo-2-(cyanomethyl)benzonitrile

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4-Bromo-2-(cyanomethyl)benzonitrile (75 g, 339 mmol) was added to 2,2-dichloroacetic acid (150 mL, 339 mmol). The resulting solution was cooled to 0° C. in an ice-water bath. HBr (27.5 g, 339 mmol) was bubbled through the cold solution until a yellow precipitate crashed out of solution resulting in a yellow slurry. HBr was bubbled through the slurry for an additional 5 minutes. The solution was allowed to warm to room temperature over 1 hour. The slurry was then re-cooled to 0° C. in an ice-water bath and diethyl ether (200 mL) was added. The mixture was stirred for 20 minutes at 5° C. The product was recovered as a yellow solid by filtration (42 g, 41%). LCMS (API-ES) m/z: 303 (M+H+). resulting in a yellow slurry HBr was bubbled through the slurry for an additional 5 minutes to warm to room temperature over 1 hour The slurry was then re-cooled to 0° C. in an ice-water bath diethyl ether (200 mL) was added The product was recovered as a yellow solid by filtration (42 g, 41%)

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Sodium hydride (47.2 g, 1.18 mol) was suspended in 320 mL DMSO and cooled to 0° C. in an ice-water bath. The mixture became viscous as the DMSO began to freeze. Methyl cyanoacetate (104 mL, 1.18 mol) was added slowly causing a slight temperature increase and thus a more easily stirrable solution. The mixture was stirred for 30 minutes at room temperature. 4-Bromo-2-fluorobenzonitrile (118 g, 590 mmol) (commercially available from Acros Organics (Order Number 29049)) was added via cannula as a solution in 500 mL DMSO. The mixture was heated to an internal temperature of 90° C. The mixture was cooled and allowed to stand overnight. 1.2 L of water was added to the reaction mixture. The mixture was heated to an internal temperature of 104° C. over 3 hours. 2.3 L of water was added and the mixture was heated at reflux 16 hours. The mixture was cooled to 5° C. and 700 mL of 0.2N HCl was added. The mixture was allowed to stir at 5° C. for 30 minutes. The resulting precipitate was filtered, washed with water, and dried to provide the product (102 g, 78%). LCMS (API-ES) m/z: 223, 221 (M+H+). increase The mixture was heated to an internal temperature of 90° C The mixture was cooled to stand overnight The mixture was heated to an internal temperature of 104° C. over 3 hours the mixture was heated at reflux 16 hours The mixture was cooled to 5° C. to stir at 5° C. for 30 minutes The resulting precipitate was filtered washed with water dried

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Sodium hydride (47.2 g, 1.18 mol) was suspended in 320 mL DMSO and cooled to 0° C. in an ice-water bath. The mixture became viscous as the DMSO began to freeze. Methyl cyanoacetate (104 mL, 1.18 mol) was added slowly causing a slight temperature increase and thus a more easily stirrable solution. The mixture was stirred for 30 minutes at room temperature. 4-Bromo-2-fluorobenzonitrile (118 g, 590 mmol) (commercially available from Acros Organics (Order Number 29049)) was added via cannula as a solution in 500 mL DMSO. The mixture was heated to an internal temperature of 90° C. The mixture was cooled and allowed to stand overnight. 1.2 L of water was added to the reaction mixture. The mixture was heated to an internal temperature of 104° C. over 3 hours. 2.3 L of water was added and the mixture was heated at reflux 16 hours. The mixture was cooled to 5° C. and 700 mL of 0.2N HCl was added. The mixture was allowed to stir at 5° C. for 30 minutes. The resulting precipitate was filtered, washed with water, and dried to provide the product (102 g, 78%). LCMS (API-ES) m/z: 223, 221 (M+H+). increase The mixture was heated to an internal temperature of 90° C The mixture was cooled to stand overnight The mixture was heated to an internal temperature of 104° C. over 3 hours the mixture was heated at reflux 16 hours The mixture was cooled to 5° C. to stir at 5° C. for 30 minutes The resulting precipitate was filtered washed with water dried

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4-Bromo-2-(cyanomethyl)benzonitrile (75 g, 339 mmol) was added to 2,2-dichloroacetic acid (150 mL, 339 mmol). The resulting solution was cooled to 0° C. in an ice-water bath. HBr (27.5 g, 339 mmol) was bubbled through the cold solution until a yellow precipitate crashed out of solution, resulting in a yellow slurry. HBr was bubbled through the slurry for an additional 5 minutes. The solution was allowed to warm to room temperature over 1 hour. The slurry was then cooled to 0° C. in an ice-water bath and diethyl ether (200 mL) was added. The mixture was stirred for 20 minutes at 5° C. The product was recovered as a yellow solid by filtration (42 g, 41%). LCMS (API-ES) m/z: 303 (M+H+). resulting in a yellow slurry HBr was bubbled through the slurry for an additional 5 minutes to warm to room temperature over 1 hour The slurry was then cooled to 0° C. in an ice-water bath diethyl ether (200 mL) was added The product was recovered as a yellow solid by filtration (42 g, 41%)

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Sodium hydride (47.2 g, 1.18 mol) was suspended in 320 mL DMSO and cooled to 0° C. in an ice-water bath. The mixture became viscous as the DMSO began to freeze. Methyl cyanoacetate (104 mL, 1.18 mol) was added slowly causing a slight temperature increase and thus a more easily stirrable solution. The mixture was stirred for 30 minutes at room temperature. 4-Bromo-2-fluorobenzonitrile (118 g, 590 mmol) (commercially available from Acros Organics (Order Number 29049)) was added via cannula as a solution in 500 mL DMSO. The mixture was heated to an internal temperature of 90° C. The mixture was cooled and allowed to stand overnight. 1.2 L of water was added to the reaction mixture. The mixture was heated to an internal temperature of 104° C. over 3 hours. 2.3 L of water were added, and the mixture was heated at reflux 16 hours. The mixture was cooled to 5° C. HCl (700 mL, 0.2 N) was added, and the mixture was allowed to stir at 5° C. for 30 minutes. The resulting precipitate was filtered, washed with water, and dried to provide the product (102 g, 78%). LCMS (API-ES) m/z: 223, 221 (M+H+). increase The mixture was heated to an internal temperature of 90° C The mixture was cooled to stand overnight The mixture was heated to an internal temperature of 104° C. over 3 hours the mixture was heated at reflux 16 hours The mixture was cooled to 5° C to stir at 5° C. for 30 minutes The resulting precipitate was filtered washed with water dried

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4-Bromo-2-(cyanomethyl)benzonitrile (75 g, 339 mmol) was added to 2,2-dichloroacetic acid (150 mL, 339 mmol). The resulting solution was cooled to 0° C. in an ice-water bath. HBr (27.5 g, 339 mmol) was bubbled through the cold solution until a yellow precipitate crashed out of solution resulting in a yellow slurry. HBr was bubbled through the slurry for an additional 5 minutes. The solution was allowed to warm to room temperature over 1 hour. The slurry was then re-cooled to 0° C. in an ice-water bath and diethyl ether (200 mL) was added. The mixture was stirred for 20 minutes at 5° C. The product was recovered as a yellow solid by filtration (42 g, 41%). LCMS (API-ES) m/z: 303 (M+H+). resulting in a yellow slurry HBr was bubbled through the slurry for an additional 5 minutes to warm to room temperature over 1 hour The slurry was then re-cooled to 0° C. in an ice-water bath diethyl ether (200 mL) was added The product was recovered as a yellow solid by filtration (42 g, 41%)

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Sodium hydride (47.2 g, 1.18 mol) was suspended in 320 mL DMSO and cooled to 0° C. in an ice-water bath. The mixture became viscous as the DMSO began to freeze. Methyl cyanoacetate (104 mL, 1.18 mol) was added slowly causing a slight temperature increase and thus a more easily stirrable solution. The mixture was stirred for 30 minutes at room temperature. 4-Bromo-2-fluorobenzonitrile (118 g, 590 mmol) (commercially available from Acros Organics (Order Number 29049)) was added via cannula as a solution in 500 mL DMSO. The mixture was heated to an internal temperature of 90° C. The mixture was cooled and allowed to stand overnight. 1.2 L of water was added to the reaction mixture. The mixture was heated to an internal temperature of 104° C. over 3 hours. 2.3 L of water was added and the mixture was heated at reflux 16 hours. The mixture was cooled to 5° C. and 700 mL of 0.2N HCl was added. The mixture was allowed to stir at 5° C. for 30 minutes. The resulting precipitate was filtered, washed with water, and dried to provide the product (102 g, 78%). LCMS (API-ES) m/z: 223, 221 (M+H+). increase The mixture was heated to an internal temperature of 90° C The mixture was cooled to stand overnight The mixture was heated to an internal temperature of 104° C. over 3 hours the mixture was heated at reflux 16 hours The mixture was cooled to 5° C. to stir at 5° C. for 30 minutes The resulting precipitate was filtered washed with water dried