4-BROMO-3-FORMYL-BENZONITRILE

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

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

Conditions: temp:-25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Diethyl (4-trifluoromethoxybenzyl)phosphonate (7.8 g) was dissolved in 100 mL of DMF, 5.0 g of 4-bromo-3-formyl-benzonitrile was added, and the mixture was cooled to −25° C. Potassium tert-butoxide (6.4 g) was added, and the mixture was stirred for 2 hours at −25° C. To the reaction mixture, 100 mL of a saturated aqueous solution of ammonium chloride and 100 mL of water were added, and the mixture was extracted 3 times with ethyl acetate (100 mL). The respective organic layers were combined, whereafter the combined organic layer was washed with water and a saturated aqueous solution of sodium chloride, and dried over magnesium sulfate. The magnesium sulfate was separated by filtration, and the filtrate was concentrated under reduced pressure. The residue was subjected to 100 g silica gel column chromatography to obtain 3.9 g of 4-bromo-3-[2-(4-trifluoromethoxy-phenyl)-vinyl]-benzonitrile as a crude product with the use of an eluant (ethyl acetate and n-hexane, 1:10). the mixture was extracted 3 times with ethyl acetate (100 mL) was washed with water a saturated aqueous solution of sodium chloride, and dried over magnesium sulfate The magnesium sulfate was separated by filtration the filtrate was concentrated under reduced pressure

Conditions: temp:-25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Diethyl (4-trifluoromethoxybenzyl)phosphonate (7.8 g) was dissolved in 100 mL of DMF, 5.0 g of 4-bromo-3-formyl-benzonitrile was added, and the mixture was cooled to −25° C. Potassium tert-butoxide (6.4 g) was added, and the mixture was stirred for 2 hours at −25° C. To the reaction mixture, 100 mL of a saturated aqueous solution of ammonium chloride and 100 mL of water were added, and the mixture was extracted 3 times with ethyl acetate (100 mL). The respective organic layers were combined, whereafter the combined organic layer was washed with water and a saturated aqueous solution of sodium chloride, and dried over magnesium sulfate. The magnesium sulfate was separated by filtration, and the filtrate was concentrated under reduced pressure. The residue was subjected to 100 g silica gel column chromatography to obtain 3.9 g of 4-bromo-3-[2-(4-trifluoromethoxy-phenyl)-vinyl]-benzonitrile as a crude product with the use of an eluant (ethyl acetate and n-hexane, 1:10). the mixture was extracted 3 times with ethyl acetate (100 mL) was washed with water a saturated aqueous solution of sodium chloride, and dried over magnesium sulfate The magnesium sulfate was separated by filtration the filtrate was concentrated under reduced pressure

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

Procedure: To 4-bromo-3-formyl-benzonitrile (2.42 g, 11.5 mmol) in MeOH (450 mL) was added benzylamine (1.88 mL, 17.3 mmol) and sodium cyanoborohydride (1.09 g, 17.3 mmol). Acetic acid (0.99 mL, 17.3 mmol) was added dropwise, and the reaction was stirred at room temperature overnight. The mixture was quenched with H2O and extracted with EtOAc. The combined organic layers were dried, concentrated, and purified by silica gel chromatography (0-30% EtOAc in hexanes) to give 3-(benzylamino-methyl)-4-bromo-benzonitrile. The mixture was quenched with H2O extracted with EtOAc The combined organic layers were dried concentrated purified by silica gel chromatography (0-30% EtOAc in hexanes)

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

Procedure: To 4-bromo-3-formyl-benzonitrile (2.42 g, 11.5 mmol) in MeOH (450 mL) was added benzylamine (1.88 mL, 17.3 mmol) and sodium cyanoborohydride (1.09 g, 17.3 mmol). Acetic acid (0.99 mL, 17.3 mmol) was added dropwise, and the reaction was stirred at room temperature overnight. The mixture was quenched with H2O and extracted with EtOAc. The combined organic layers were dried, concentrated, and purified by silica gel chromatography (0-30% EtOAc in hexanes) to give 3-(benzylamino-methyl)-4-bromo-benzonitrile. The mixture was quenched with H2O extracted with EtOAc The combined organic layers were dried concentrated purified by silica gel chromatography (0-30% EtOAc in hexanes)

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Bromo-3-dibromomethyl-benzonitrile (5.66 g, 16 mmol) was dissolved in EtOH (150 mL) and heated to 60° C. Silver nitrate (6.80 g, 40 mmol), prepared as a solution in H2O (40 mL), was added dropwise, and the reaction was heated to 75° C. and stirred overnight. The organic layer was decanted, concentrated, and filtered, and the residue was partitioned between EtOAc and H2O. The product was extracted with EtOAc, and the combined organic layers were concentrated and purified by silica gel chromatography (0-30% EtOAc in hexanes) to give 4-bromo-3-formyl-benzonitrile. was added dropwise the reaction was heated to 75° C. The organic layer was decanted concentrated filtered the residue was partitioned between EtOAc and H2O The product was extracted with EtOAc the combined organic layers were concentrated purified by silica gel chromatography (0-30% EtOAc in hexanes)

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

Conditions: temp:-25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Diethyl (4-trifluoromethoxybenzyl)phosphonate (7.8 g) was dissolved in 100 mL of DMF, 5.0 g of 4-bromo-3-formyl-benzonitrile was added, and the mixture was cooled to −25° C. Potassium tert-butoxide (6.4 g) was added, and the mixture was stirred for 2 hours at −25° C. To the reaction mixture, 100 mL of a saturated aqueous solution of ammonium chloride and 100 mL of water were added, and the mixture was extracted 3 times with ethyl acetate (100 mL). The respective organic layers were combined, whereafter the combined organic layer was washed with water and a saturated aqueous solution of sodium chloride, and dried over magnesium sulfate. The magnesium sulfate was separated by filtration, and the filtrate was concentrated under reduced pressure. The residue was subjected to 100 g silica gel column chromatography to obtain 3.9 g of 4-bromo-3-[2-(4-trifluoromethoxy-phenyl)-vinyl]-benzonitrile as a crude product with the use of an eluant (ethyl acetate and n-hexane, 1:10). the mixture was extracted 3 times with ethyl acetate (100 mL) was washed with water a saturated aqueous solution of sodium chloride, and dried over magnesium sulfate The magnesium sulfate was separated by filtration the filtrate was concentrated under reduced pressure

Conditions: temp:-25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Diethyl (4-trifluoromethoxybenzyl)phosphonate (7.8 g) was dissolved in 100 mL of DMF, 5.0 g of 4-bromo-3-formyl-benzonitrile was added, and the mixture was cooled to −25° C. Potassium tert-butoxide (6.4 g) was added, and the mixture was stirred for 2 hours at −25° C. To the reaction mixture, 100 mL of a saturated aqueous solution of ammonium chloride and 100 mL of water were added, and the mixture was extracted 3 times with ethyl acetate (100 mL). The respective organic layers were combined, whereafter the combined organic layer was washed with water and a saturated aqueous solution of sodium chloride, and dried over magnesium sulfate. The magnesium sulfate was separated by filtration, and the filtrate was concentrated under reduced pressure. The residue was subjected to 100 g silica gel column chromatography to obtain 3.9 g of 4-bromo-3-[2-(4-trifluoromethoxy-phenyl)-vinyl]-benzonitrile as a crude product with the use of an eluant (ethyl acetate and n-hexane, 1:10). the mixture was extracted 3 times with ethyl acetate (100 mL) was washed with water a saturated aqueous solution of sodium chloride, and dried over magnesium sulfate The magnesium sulfate was separated by filtration the filtrate was concentrated under reduced pressure

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

Procedure: To 4-bromo-3-formyl-benzonitrile (2.42 g, 11.5 mmol) in MeOH (450 mL) was added benzylamine (1.88 mL, 17.3 mmol) and sodium cyanoborohydride (1.09 g, 17.3 mmol). Acetic acid (0.99 mL, 17.3 mmol) was added dropwise, and the reaction was stirred at room temperature overnight. The mixture was quenched with H2O and extracted with EtOAc. The combined organic layers were dried, concentrated, and purified by silica gel chromatography (0-30% EtOAc in hexanes) to give 3-(benzylamino-methyl)-4-bromo-benzonitrile. The mixture was quenched with H2O extracted with EtOAc The combined organic layers were dried concentrated purified by silica gel chromatography (0-30% EtOAc in hexanes)

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Bromo-3-dibromomethyl-benzonitrile (5.66 g, 16 mmol) was dissolved in EtOH (150 mL) and heated to 60° C. Silver nitrate (6.80 g, 40 mmol), prepared as a solution in H2O (40 mL), was added dropwise, and the reaction was heated to 75° C. and stirred overnight. The organic layer was decanted, concentrated, and filtered, and the residue was partitioned between EtOAc and H2O. The product was extracted with EtOAc, and the combined organic layers were concentrated and purified by silica gel chromatography (0-30% EtOAc in hexanes) to give 4-bromo-3-formyl-benzonitrile. was added dropwise the reaction was heated to 75° C. The organic layer was decanted concentrated filtered the residue was partitioned between EtOAc and H2O The product was extracted with EtOAc the combined organic layers were concentrated purified by silica gel chromatography (0-30% EtOAc in hexanes)