2-(2-bromo-4-chlorophenyl)acetonitrile

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

Procedure: A portion of 2-(2-bromo-4-chlorophenyl)acetonitrile (7.1 g; 39.1 mmol) was directly dissolved in borane solution (78.2 mL of a 1.0 M solution in tetrahydrofuran; 78.2 mmol), and the resulting solution was stirred and heated to reflux. After refluxing for a total of 90 minutes, the heat was removed and the solution was allowed to cool for a few minutes, and then 16 mL of methanol was carefully added to quench the solution. The resulting solution was again heated to reflux for 30 minutes. The solvent was then evaporated, and the residue was partitioned between 200 mL of 1M HCl (aq.) and 200 mL ether. The aqueous layer was filtered to remove a small amount of suspended insoluble material, and the pH of the filtrate was adjusted to pH>12 by the addition of 42% NaOH (aq.). The filtrate was then extracted with 200 mL dichloromethane. The organic layer was dried over sodium sulfate and evaporated to give 3.89 g of 2-(4-chloro-2-methoxyphenyl)ethanamine as a colorless liquid. MS (apci, pos) m/z=186. heated to reflux After refluxing for a total of 90 minutes the heat was removed to cool for a few minutes 16 mL of methanol was carefully added to quench the solution The resulting solution was again heated to reflux for 30 minutes The solvent was then evaporated the residue was partitioned between 200 mL of 1M HCl (aq.) and 200 mL ether The aqueous layer was filtered to remove a small amount of suspended insoluble material the pH of the filtrate was adjusted to pH>12 by the addition of 42% NaOH (aq.) The filtrate was then extracted with 200 mL dichloromethane The organic layer was dried over sodium sulfate evaporated

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

Procedure: A mixture of 2-bromo-1-(bromomethyl)-4-chlorobenzene (9.8 g; 34.5 mmol) and sodium cyanide (2.0 g; 41.4 mmol) in 15 mL of 95% ethanol and 2.5 mL water was stirred and heated to reflux. After 30 minutes, the solvent was evaporated and the residue was partitioned between 100 mL ether and 50 mL water. The organic layer was dried over sodium sulfate and evaporated. The residual solid was washed out of the flask with hexane and collected by filtration, washed with hexane, and air-dried on the filter to give 4.82 g of 2-(2-bromo-4-chlorophenyl)acetonitrile as a light yellow solid. heated to reflux the solvent was evaporated the residue was partitioned between 100 mL ether and 50 mL water The organic layer was dried over sodium sulfate evaporated The residual solid was washed out of the flask with hexane collected by filtration washed with hexane air-dried on the filter

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

Procedure: A portion of 2-(2-bromo-4-chlorophenyl)acetonitrile (7.1 g; 39.1 mmol) was directly dissolved in borane solution (78.2 mL of a 1.0 M solution in tetrahydrofuran; 78.2 mmol), and the resulting solution was stirred and heated to reflux. After refluxing for a total of 90 minutes, the heat was removed and the solution was allowed to cool for a few minutes, and then 16 mL of methanol was carefully added to quench the solution. The resulting solution was again heated to reflux for 30 minutes. The solvent was then evaporated, and the residue was partitioned between 200 mL of 1M HCl (aq.) and 200 mL ether. The aqueous layer was filtered to remove a small amount of suspended insoluble material, and the pH of the filtrate was adjusted to pH>12 by the addition of 42% NaOH (aq.). The filtrate was then extracted with 200 mL dichloromethane. The organic layer was dried over sodium sulfate and evaporated to give 3.89 g of 2-(4-chloro-2-methoxyphenyl)ethanamine as a colorless liquid. MS (apci, pos) m/z=186. heated to reflux After refluxing for a total of 90 minutes the heat was removed to cool for a few minutes 16 mL of methanol was carefully added to quench the solution The resulting solution was again heated to reflux for 30 minutes The solvent was then evaporated the residue was partitioned between 200 mL of 1M HCl (aq.) and 200 mL ether The aqueous layer was filtered to remove a small amount of suspended insoluble material the pH of the filtrate was adjusted to pH>12 by the addition of 42% NaOH (aq.) The filtrate was then extracted with 200 mL dichloromethane The organic layer was dried over sodium sulfate evaporated

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

Procedure: A mixture of 2-bromo-1-(bromomethyl)-4-chlorobenzene (9.8 g; 34.5 mmol) and sodium cyanide (2.0 g; 41.4 mmol) in 15 mL of 95% ethanol and 2.5 mL water was stirred and heated to reflux. After 30 minutes, the solvent was evaporated and the residue was partitioned between 100 mL ether and 50 mL water. The organic layer was dried over sodium sulfate and evaporated. The residual solid was washed out of the flask with hexane and collected by filtration, washed with hexane, and air-dried on the filter to give 4.82 g of 2-(2-bromo-4-chlorophenyl)acetonitrile as a light yellow solid. heated to reflux the solvent was evaporated the residue was partitioned between 100 mL ether and 50 mL water The organic layer was dried over sodium sulfate evaporated The residual solid was washed out of the flask with hexane collected by filtration washed with hexane air-dried on the filter

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

Procedure: A mixture of 2-bromo-1-(bromomethyl)-4-chlorobenzene (9.8 g; 34.5 mmol) and sodium cyanide (2.0 g; 41.4 mmol) in 15 mL of 95% ethanol and 2.5 mL water was stirred and heated to reflux. After 30 minutes, the solvent was evaporated and the residue was partitioned between 100 mL ether and 50 mL water. The organic layer was dried over sodium sulfate and evaporated. The residual solid was washed out of the flask with hexane and collected by filtration, washed with hexane, and air-dried on the filter to give 4.82 g of 2-(2-bromo-4-chlorophenyl)acetonitrile as a light yellow solid. heated to reflux the solvent was evaporated the residue was partitioned between 100 mL ether and 50 mL water The organic layer was dried over sodium sulfate evaporated The residual solid was washed out of the flask with hexane collected by filtration washed with hexane air-dried on the filter

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

Procedure: A portion of 2-(2-bromo-4-chlorophenyl)acetonitrile (7.1 g; 39.1 mmol) was directly dissolved in borane solution (78.2 mL of a 1.0 M solution in tetrahydrofuran; 78.2 mmol), and the resulting solution was stirred and heated to reflux. After refluxing for a total of 90 minutes, the heat was removed and the solution was allowed to cool for a few minutes, and then 16 mL of methanol was carefully added to quench the solution. The resulting solution was again heated to reflux for 30 minutes. The solvent was then evaporated, and the residue was partitioned between 200 mL of 1M HCl (aq.) and 200 mL ether. The aqueous layer was filtered to remove a small amount of suspended insoluble material, and the pH of the filtrate was adjusted to pH>12 by the addition of 42% NaOH (aq.). The filtrate was then extracted with 200 mL dichloromethane. The organic layer was dried over sodium sulfate and evaporated to give 3.89 g of 2-(4-chloro-2-methoxyphenyl)ethanamine as a colorless liquid. MS (apci, pos) m/z=186. heated to reflux After refluxing for a total of 90 minutes the heat was removed to cool for a few minutes 16 mL of methanol was carefully added to quench the solution The resulting solution was again heated to reflux for 30 minutes The solvent was then evaporated the residue was partitioned between 200 mL of 1M HCl (aq.) and 200 mL ether The aqueous layer was filtered to remove a small amount of suspended insoluble material the pH of the filtrate was adjusted to pH>12 by the addition of 42% NaOH (aq.) The filtrate was then extracted with 200 mL dichloromethane The organic layer was dried over sodium sulfate evaporated

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

Procedure: A mixture of 2-bromo-1-(bromomethyl)-4-chlorobenzene (9.8 g; 34.5 mmol) and sodium cyanide (2.0 g; 41.4 mmol) in 15 mL of 95% ethanol and 2.5 mL water was stirred and heated to reflux. After 30 minutes, the solvent was evaporated and the residue was partitioned between 100 mL ether and 50 mL water. The organic layer was dried over sodium sulfate and evaporated. The residual solid was washed out of the flask with hexane and collected by filtration, washed with hexane, and air-dried on the filter to give 4.82 g of 2-(2-bromo-4-chlorophenyl)acetonitrile as a light yellow solid. heated to reflux the solvent was evaporated the residue was partitioned between 100 mL ether and 50 mL water The organic layer was dried over sodium sulfate evaporated The residual solid was washed out of the flask with hexane collected by filtration washed with hexane air-dried on the filter

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

Procedure: A mixture of 2-bromo-1-(bromomethyl)-4-chlorobenzene (9.8 g; 34.5 mmol) and sodium cyanide (2.0 g; 41.4 mmol) in 15 mL of 95% ethanol and 2.5 mL water was stirred and heated to reflux. After 30 minutes, the solvent was evaporated and the residue was partitioned between 100 mL ether and 50 mL water. The organic layer was dried over sodium sulfate and evaporated. The residual solid was washed out of the flask with hexane and collected by filtration, washed with hexane, and air-dried on the filter to give 4.82 g of 2-(2-bromo-4-chlorophenyl)acetonitrile as a light yellow solid. heated to reflux the solvent was evaporated the residue was partitioned between 100 mL ether and 50 mL water The organic layer was dried over sodium sulfate evaporated The residual solid was washed out of the flask with hexane collected by filtration washed with hexane air-dried on the filter

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

Procedure: To a stirred suspension of NH4Cl (9.241 g, 169.565 mmol) in dry toluene (120 mL) was added tri-methyl aluminum (2M) (45.23 mL, 90.435 mmol) at 5° C. the reaction mixture was warmed to room temperature and the reaction mixture was stirred for 2 h. A solution of (2-bromo-4-chlorophenyl)-acetonitrile (374) (13 g, 56.522 mmol) in toluene (30 mL) was added to the above reaction mixture and the reaction mixture was stirred for 14 h at 80° C. while silica thin layer chromatography was performed (10% methanol in dichloromethane; Rf=0.2). After completion of the reaction, the reaction mixture was quenched with a suspension of silica gel (20 g) in chloroform (200 mL) and the reaction mixture was stirred for half an hour at room temperature and filtered. The silica gel was washed with methanol (100 mL) and the combined filtrate was concentrated under reduced pressure to get 2-(2-bromo-4-chlorophenyl)-acetamidine hydrochloride (375) (14.0 g, 87.68%) as a white solid. the reaction mixture was stirred for 14 h at 80° C. while silica thin layer chromatography After completion of the reaction the reaction mixture was quenched with a suspension of silica gel (20 g) in chloroform (200 mL) the reaction mixture was stirred for half an hour at room temperature filtered The silica gel was washed with methanol (100 mL) the combined filtrate was concentrated under reduced pressure

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

Procedure: A portion of 2-(2-bromo-4-chlorophenyl)acetonitrile (7.1 g; 39.1 mmol) was directly dissolved in borane solution (78.2 mL of a 1.0 M solution in tetrahydrofuran; 78.2 mmol), and the resulting solution was stirred and heated to reflux. After refluxing for a total of 90 minutes, the heat was removed and the solution was allowed to cool for a few minutes, and then 16 mL of methanol was carefully added to quench the solution. The resulting solution was again heated to reflux for 30 minutes. The solvent was then evaporated, and the residue was partitioned between 200 mL of 1M HCl (aq.) and 200 mL ether. The aqueous layer was filtered to remove a small amount of suspended insoluble material, and the pH of the filtrate was adjusted to pH>12 by the addition of 42% NaOH (aq.). The filtrate was then extracted with 200 mL dichloromethane. The organic layer was dried over sodium sulfate and evaporated to give 3.89 g of 2-(4-chloro-2-methoxyphenyl)ethanamine as a colorless liquid. MS (apci, pos) m/z=186. heated to reflux After refluxing for a total of 90 minutes the heat was removed to cool for a few minutes 16 mL of methanol was carefully added to quench the solution The resulting solution was again heated to reflux for 30 minutes The solvent was then evaporated the residue was partitioned between 200 mL of 1M HCl (aq.) and 200 mL ether The aqueous layer was filtered to remove a small amount of suspended insoluble material the pH of the filtrate was adjusted to pH>12 by the addition of 42% NaOH (aq.) The filtrate was then extracted with 200 mL dichloromethane The organic layer was dried over sodium sulfate evaporated

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

Procedure: A mixture of 2-bromo-1-(bromomethyl)-4-chlorobenzene (9.8 g; 34.5 mmol) and sodium cyanide (2.0 g; 41.4 mmol) in 15 mL of 95% ethanol and 2.5 mL water was stirred and heated to reflux. After 30 minutes, the solvent was evaporated and the residue was partitioned between 100 mL ether and 50 mL water. The organic layer was dried over sodium sulfate and evaporated. The residual solid was washed out of the flask with hexane and collected by filtration, washed with hexane, and air-dried on the filter to give 4.82 g of 2-(2-bromo-4-chlorophenyl)acetonitrile as a light yellow solid. heated to reflux the solvent was evaporated the residue was partitioned between 100 mL ether and 50 mL water The organic layer was dried over sodium sulfate evaporated The residual solid was washed out of the flask with hexane collected by filtration washed with hexane air-dried on the filter

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

Procedure: A portion of 2-(2-bromo-4-chlorophenyl)acetonitrile (7.1 g; 39.1 mmol) was directly dissolved in borane solution (78.2 mL of a 1.0 M solution in tetrahydrofuran; 78.2 mmol), and the resulting solution was stirred and heated to reflux. After refluxing for a total of 90 minutes, the heat was removed and the solution was allowed to cool for a few minutes, and then 16 mL of methanol was carefully added to quench the solution. The resulting solution was again heated to reflux for 30 minutes. The solvent was then evaporated, and the residue was partitioned between 200 mL of 1M HCl (aq.) and 200 mL ether. The aqueous layer was filtered to remove a small amount of suspended insoluble material, and the pH of the filtrate was adjusted to pH>12 by the addition of 42% NaOH (aq.). The filtrate was then extracted with 200 mL dichloromethane. The organic layer was dried over sodium sulfate and evaporated to give 3.89 g of 2-(4-chloro-2-methoxyphenyl)ethanamine as a colorless liquid. MS (apci, pos) m/z=186. heated to reflux After refluxing for a total of 90 minutes the heat was removed to cool for a few minutes 16 mL of methanol was carefully added to quench the solution The resulting solution was again heated to reflux for 30 minutes The solvent was then evaporated the residue was partitioned between 200 mL of 1M HCl (aq.) and 200 mL ether The aqueous layer was filtered to remove a small amount of suspended insoluble material the pH of the filtrate was adjusted to pH>12 by the addition of 42% NaOH (aq.) The filtrate was then extracted with 200 mL dichloromethane The organic layer was dried over sodium sulfate evaporated