methyl 4-bromo-2,6-dichlorobenzoate

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

Procedure: To a solution of 2,6-dichloro-4-bromobenzoic acid methyl ester (0.55 g) in THF (10 mL) was added benzeneboronic acid (1.30 g), Pd(PPh3)4 (0.16 g) and 2M Na2CO3 (5 mL). The mixture was refluxed for 4 h under N2. After cooling, the mixture was diluted with EtOAc and washed with water and brine. The organic layer was dried (Na2SO4), filtered, and concentrated. The residue was purified by preparative TLC (silica gel; eluent: hexane to EtOAc/hexane 1/1) to yield crude 2,6-dichloro-4-phenylbenzoic acid methyl ester (0.57 g). ESMS: m/z 281 (MH+). The mixture was refluxed for 4 h under N2 After cooling washed with water and brine The organic layer was dried (Na2SO4) filtered concentrated The residue was purified by preparative TLC (silica gel; eluent: hexane to EtOAc/hexane 1/1)

Conditions: temp:2.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Amino-2,6-dichlorobenzoic acid methyl ester (1.00 g) was suspended in 40% aq. HBr and the mixture was cooled lto 0-5° C. After NaNO2 (376 mg) was added in small portions, the mixture was stirred for about 5 min. Copper (100 mg) was added and the mixture was warmed up to 100° C. The mixture was then stirred at 100° C. for 30 min, diluted with water and extracted with AcOEt. The extract was dried (MgSO4), filtered and evaporated. The residue was purified by column chromatography (silica gel; eluent: hexane and AcOEt 50:1) to give 4-bromo-2,6-dichlorobenzoic acid methyl ester (1.07 g). the mixture was warmed up to 100° C The mixture was then stirred at 100° C. for 30 min extracted with AcOEt The extract was dried (MgSO4) filtered evaporated The residue was purified by column chromatography (silica gel; eluent: hexane and AcOEt 50:1)

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

Procedure: To a solution of 2,6-dichloro-4-bromobenzoic acid methyl ester (0.55 g) in THF (10 mL) was added benzeneboronic acid (1.30 g), Pd(PPh3)4 (0.16 g) and 2M Na2CO3 (5 mL). The mixture was refluxed for 4 h under N2. After cooling, the mixture was diluted with EtOAc and washed with water and brine. The organic layer was dried (Na2SO4), filtered, and concentrated. The residue was purified by preparative TLC (silica gel; eluent: hexane to EtOAc/hexane 1/1) to yield crude 2,6-dichloro-4-phenylbenzoic acid methyl ester (0.57 g). ESMS: m/z 281 (MH+). The mixture was refluxed for 4 h under N2 After cooling washed with water and brine The organic layer was dried (Na2SO4) filtered concentrated The residue was purified by preparative TLC (silica gel; eluent: hexane to EtOAc/hexane 1/1)

Conditions: temp:2.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Amino-2,6-dichlorobenzoic acid methyl ester (1.00 g) was suspended in 40% aq. HBr and the mixture was cooled 1 to 0-5° C. After NaNO2 (376 mg) was added in small portions, the mixture was stirred for about 5 min. Copper (100 mg) was added and the mixture was warmed up to 100° C. The mixture was then stirred at 100° C. for 30 min, diluted with water and extracted with AcOEt. The extract was dried (MgSO4), filtered and evaporated. The residue was purified by column chromatography (silica gel; eluent: hexane and AcOEt 50:1) to give 4-bromo-2,6-dichlorobenzoic acid methyl ester (1.07 g). the mixture was warmed up to 100° C The mixture was then stirred at 100° C. for 30 min extracted with AcOEt The extract was dried (MgSO4) filtered evaporated The residue was purified by column chromatography (silica gel; eluent: hexane and AcOEt 50:1)

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

Procedure: To a solution of 2,6-dichloro-4-bromobenzoic acid methyl ester (0.55 g) in THF (10 mL) was added benzeneboronic acid (1.30 g), Pd(PPh3)4 (0.16 g) and 2M Na2CO3 (5 mL). The mixture was refluxed for 4 h under N2. After cooling, the mixture was diluted with EtOAc and washed with water and brine. The organic layer was dried (Na2SO4), filtered, and concentrated. The residue was purified by preparative TLC (silica gel; eluent: hexane to EtOAc/hexane 1/1) to yield crude 2,6-dichloro-4-phenylbenzoic acid methyl ester (0.57 g). ESMS: m/z 281 (MH+). The mixture was refluxed for 4 h under N2 After cooling washed with water and brine The organic layer was dried (Na2SO4) filtered concentrated The residue was purified by preparative TLC (silica gel; eluent: hexane to EtOAc/hexane 1/1)

Conditions: temp:2.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Amino-2,6-dichlorobenzoic acid methyl ester (1.00 g) was suspended in 40% aq. HBr and the mixture was cooled lto 0-5° C. After NaNO2 (376 mg) was added in small portions, the mixture was stirred for about 5 min. Copper (100 mg) was added and the mixture was warmed up to 100° C. The mixture was then stirred at 100° C. for 30 min, diluted with water and extracted with AcOEt. The extract was dried (MgSO4), filtered and evaporated. The residue was purified by column chromatography (silica gel; eluent: hexane and AcOEt 50:1) to give 4-bromo-2,6-dichlorobenzoic acid methyl ester (1.07 g). the mixture was warmed up to 100° C The mixture was then stirred at 100° C. for 30 min extracted with AcOEt The extract was dried (MgSO4) filtered evaporated The residue was purified by column chromatography (silica gel; eluent: hexane and AcOEt 50:1)

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

Procedure: To a solution of 2,6-dichloro-4-bromobenzoic acid methyl ester (0.55 g) in THF (10 mL) was added benzeneboronic acid (1.30 g), Pd(PPh3)4 (0.16 g) and 2M Na2CO3 (5 mL). The mixture was refluxed for 4 h under N2. After cooling, the mixture was diluted with EtOAc and washed with water and brine. The organic layer was dried (Na2SO4), filtered, and concentrated. The residue was purified by preparative TLC (silica gel; eluent: hexane to EtOAc/hexane 1/1) to yield crude 2,6-dichloro-4-phenylbenzoic acid methyl ester (0.57 g). ESMS: m/z 281 (MH+). The mixture was refluxed for 4 h under N2 After cooling washed with water and brine The organic layer was dried (Na2SO4) filtered concentrated The residue was purified by preparative TLC (silica gel; eluent: hexane to EtOAc/hexane 1/1)

Conditions: temp:2.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Amino-2,6-dichlorobenzoic acid methyl ester (1.00 g) was suspended in 40% aq. HBr and the mixture was cooled lto 0-5° C. After NaNO2 (376 mg) was added in small portions, the mixture was stirred for about 5 min. Copper (100 mg) was added and the mixture was warmed up to 100° C. The mixture was then stirred at 100° C. for 30 min, diluted with water and extracted with AcOEt. The extract was dried (MgSO4), filtered and evaporated. The residue was purified by column chromatography (silica gel; eluent: hexane and AcOEt 50:1) to give 4-bromo-2,6-dichlorobenzoic acid methyl ester (1.07 g). the mixture was warmed up to 100° C The mixture was then stirred at 100° C. for 30 min extracted with AcOEt The extract was dried (MgSO4) filtered evaporated The residue was purified by column chromatography (silica gel; eluent: hexane and AcOEt 50:1)

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

Procedure: To a solution of 2,6-dichloro-4-bromobenzoic acid methyl ester (0.55 g) in THF (10 mL) was added benzeneboronic acid (1.30 g), Pd(PPh3)4 (0.16 g) and 2M Na2CO3 (5 mL). The mixture was refluxed for 4 h under N2. After cooling, the mixture was diluted with EtOAc and washed with water and brine. The organic layer was dried (Na2SO4), filtered, and concentrated. The residue was purified by preparative TLC (silica gel; eluent: hexane to EtOAc/hexane 1/1) to yield crude 2,6-dichloro-4-phenylbenzoic acid methyl ester (0.57 g). ESMS: m/z 281 (MH+). The mixture was refluxed for 4 h under N2 After cooling washed with water and brine The organic layer was dried (Na2SO4) filtered concentrated The residue was purified by preparative TLC (silica gel; eluent: hexane to EtOAc/hexane 1/1)

Conditions: temp:2.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Amino-2,6-dichlorobenzoic acid methyl ester (1.00 g) was suspended in 40% aq. HBr and the mixture was cooled 1 to 0-5° C. After NaNO2 (376 mg) was added in small portions, the mixture was stirred for about 5 min. Copper (100 mg) was added and the mixture was warmed up to 100° C. The mixture was then stirred at 100° C. for 30 min, diluted with water and extracted with AcOEt. The extract was dried (MgSO4), filtered and evaporated. The residue was purified by column chromatography (silica gel; eluent: hexane and AcOEt 50:1) to give 4-bromo-2,6-dichlorobenzoic acid methyl ester (1.07 g). the mixture was warmed up to 100° C The mixture was then stirred at 100° C. for 30 min extracted with AcOEt The extract was dried (MgSO4) filtered evaporated The residue was purified by column chromatography (silica gel; eluent: hexane and AcOEt 50:1)