2-bromo-2-(2-chlorophenyl)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: 2-(2-Chlorophenyl) acetonitrile (151.5 g, 1 mol) was heated to 110° C. in a three-necked flask, keep the temperature, bromine (176 g, 1.1 mol) was added dropwise over a period of 3 h and the mixture was reacted with constant stirring for another 3 h. The reaction mixture was cooled to below 30° C. and water (400 mL) was added and stirring continued for another 5 minutes to remove HBr and stand aside. The organic layer was separated and washed with small amount of 5% sodium bisulfite for 15 minutes with stirring. The organic layer was again separated and washed with water to near pH 7, and the brown oily product was obtained (225 g, 96% yield); bp: 107-110° C./15 mmHg. IR (cm−1): 2969, 2253, 1589, 1472, 1445, 1194, 1051, 765, 725, 646; 1HNMR (300 MHz, CDCl3): 7.83 (1H, m), 7.38-7.45 (4H, m), 5.87 (1H, s). The crude product was used directly for the next step. was added dropwise over a period of 3 h the mixture was reacted The reaction mixture was cooled to below 30° C. stirring continued for another 5 minutes to remove HBr The organic layer was separated washed with small amount of 5% sodium bisulfite for 15 minutes with stirring The organic layer was again separated washed with water the brown oily product was obtained (225 g, 96% yield)

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

Procedure: To a solution of bromo-(2-chloro-phenyl)-acetonitrile (1)(1.5 g, 6.45 mmol) in MeCN (25 mL) was added K2CO3 (1.78 g, 12.91 mmol), piperazine-1-carboxylic acid tert-butyl ester (1.32 g, 7.10 mmol) and tetrabutylammonium iodide (0.02 g, 0.06 mmol). The reaction mixture was allowed to reflux for 24 h. The reaction mixture was then diluted with EtOAc (100 mL) and washed with brine (100 mL). The organic phase was concentrated to dryness. The crude material was purified by chromatography (silica gel 60 mesh, eluting with a gradient of 5% EtOAc in hexanes to 1:1 hexanes/EtOAc) yielding 1.4 g (65%) of pure product. to reflux for 24 h washed with brine (100 mL) The organic phase was concentrated to dryness The crude material was purified by chromatography (silica gel 60 mesh eluting with a gradient of 5% EtOAc in hexanes to 1:1 hexanes/EtOAc)

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

Procedure: To a solution of 2-chlorobenzylcyanide (1.0 g, 6.60 mmol) in CCl4 (25 mL) was added N-bromosuccinamide (1.29 g, 7.26 mmol) and 2,2′-azobis-(2-methylpropionitrile) (0.05 g, 0.33 mmol). The reaction mixture was allowed to reflux for 48 h. The reaction mixture was then diluted with EtOAc (50 mL) and washed with 0.1 M NaOH (50 mL). The organic phase was concentrated to dryness yielding 1.0 g (66%) product. to reflux for 48 h washed with 0.1 M NaOH (50 mL) The organic phase was concentrated to dryness