5-bromo-2-(bromomethyl)benzonitrile

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

Conditions: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 3,4-dichlorophenol (267.1 mg, 1.639 mmol), 5-bromo-2-(bromomethyl)benzonitrile (447.3 mg, 1.627 mmol), and potassium carbonate (674.1 mg, 4.877 mmol) in acetone (20 mL) was heated to 75° C. under nitrogen for 18 hours. The reaction mixture was cooled to room temperature, diluted with EtOAc (20 mL) and filtered through arbocel. The arbocel was then washed with EtOAc (2×20 mL), and the combined organics were washed with brine (3×20 mL), dried over sodium sulphate, filtered and concentrated in vacuo to afford the title compound as a white solid (549.9 mg, 95%). The reaction mixture was cooled to room temperature filtered through arbocel The arbocel was then washed with EtOAc (2×20 mL) the combined organics were washed with brine (3×20 mL) dried over sodium sulphate filtered concentrated in vacuo

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

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

Procedure: 5-Bromo-2-bromomethylbenzonitrile (2.50 g, 9.1 mmol) is added portionwise to a stirred solution of morpholine (828 μL, 9.5 mmol) and triethylamine (1.27 mL, 9.1 mmol) in methanol (2 mL). After 4 hr, the solvent is removed and the residue is suspended in water that is made basic with sodium hydroxide and then extracted with ethyl acetate. The extract is dried, filtered, and concentrated to give 5-bromo-2-(morpholin-4-yl)methylbenzonitrile (1.90 g, 74%) as a cream solid. the solvent is removed extracted with ethyl acetate The extract is dried filtered concentrated

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

Procedure: A mixture of 5-bromo-2-methylbenzonitrile (5.0 g, 25.5 mmol), N-bromosuccinimide (4.54 g, 25.5 mmol), 2′,2′-azobis(2-methylpropionitrile) (0.05 g) and carbon tetrachloride (25 mL) is heated at reflux for 75 min. After cooling to room temperature, the solids are removed by filtration. The filtrate is concentrated and the residue purified by chromatography eluting with cyclohexane-20% ethyl acetate. Product containing fractions are combined and concentrated to afford 5-bromo-2-bromomethylbenzonitrile (2.69 g, 38%). LC/MS: MS showed no parent molecular ion peak; RT 3.52 min. is heated at reflux for 75 min the solids are removed by filtration The filtrate is concentrated the residue purified by chromatography eluting with cyclohexane-20% ethyl acetate Product containing fractions concentrated

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

Procedure: A mixture of 5-bromo-2-bromomethyl-benzonitrile (2.0 g, 7.3 mmol), morpholine (0.76 g, 8.7 mmol) and K2CO3 (1.0 g, 7.3 mmol) is stirred in 50 DMF at room temperature for 72 hours. The reaction mixture is filtered and the filtrate is dried under vacuum to yield the title compound. 1H-NMR (400 MHz; DMSO-d6): 8.11 (d, 1H), 7.90 (dd, 1H), 7.53 (d, 1H), 3.60 (s, 2H), 3.56 (t, 4H), 2.39 (t, 4H). LC-MS (m/z, ES+): 281 (MH+), Retention time: 1.79 mins (LC-MS method 2) The reaction mixture is filtered the filtrate is dried under vacuum

Conditions: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 3,4-dichlorophenol (267.1 mg, 1.639 mmol), 5-bromo-2-(bromomethyl)benzonitrile (447.3 mg, 1.627 mmol), and potassium carbonate (674.1 mg, 4.877 mmol) in acetone (20 mL) was heated to 75° C. under nitrogen for 18 hours. The reaction mixture was cooled to room temperature, diluted with EtOAc (20 mL) and filtered through arbocel. The arbocel was then washed with EtOAc (2×20 mL), and the combined organics were washed with brine (3×20 mL), dried over sodium sulphate, filtered and concentrated in vacuo to afford the title compound as a white solid (549.9 mg, 95%). The reaction mixture was cooled to room temperature filtered through arbocel The arbocel was then washed with EtOAc (2×20 mL) the combined organics were washed with brine (3×20 mL) dried over sodium sulphate filtered concentrated in vacuo