1-bromo-2-chloro-4-methylbenzene

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

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

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 4-bromo-3-chlorotoluene (4.97 g, 24.2 mmol) in DMF (25 mL) is added Pd(OAc)2 (0.54 g, 2.42 mmol), 1,3-bis(diphenylphosphino)propane (0.998 g, 2.42 mmol), triethylamine (12.5 mL) and methanol (12.5 mL). The reaction vessel is evacuated and purged three times with carbon monoxide gas. A balloon filled with carbon monoxide gas is used to maintain the carbon monoxide atmosphere. The reaction mixture is heated at 80° C. for 8 hr. After cooling H2O (50 mL) is added. The mixture is extracted with hexanes (2×50 mL). The combined organic layers are dried over Na2SO4, filtered, concentrated and chromatographed with 0–3% EtOAc in hexanes. 1.24 g (28%) of methyl 2-chloro-4-methylbenzoate is isolated as a colorless oil. EIMS m/e 184 (M+; 35Cl) and 186 (M+; 37Cl). The reaction vessel is evacuated purged three times with carbon monoxide gas A balloon filled with carbon monoxide gas to maintain the carbon monoxide atmosphere After cooling H2O (50 mL) is added The mixture is extracted with hexanes (2×50 mL) The combined organic layers are dried over Na2SO4 filtered concentrated chromatographed with 0–3% EtOAc in hexanes

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

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Add NBS (5.266 g, 23.9 mmol) and benzoyl peroxide (49 mg, 0.2 mmol) to a solution of 4-bromo-3-chlorotoluene (4.925 g, 23.9 mmol) in carbon tetrachloride (49 mL) and heat overnight at 90° C. Cool to 0° C. and filter the mixture. Concentrate the filtrate in vacuo to obtain the desired intermediate as a yellow oil (5.807 g, 85%). Cool to 0° C. filter the mixture Concentrate the filtrate in vacuo

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under an argon atmosphere, 4-bromo-3-chlorotoluene (200 g), ethyl 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (376 g), toluene (1000 ml), water (1000 ml), tripotassium phosphate (412 g) and dichlorobis(triphenylphosphine)palladium(II) (14 g) were added to a reaction vessel and the mixture was stirred at 110° C. for 2 hr. The reaction mixture was cooled to room temperature. The insoluble material was filtered off, and washed with water (500 ml) and toluene (500 ml). The filtrate was partitioned in a separatory funnel. The organic layer was washed twice with water (1000 ml), dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure to give the title compound (337 g). The obtained residue was directly used for the next reaction without further purification. The reaction mixture was cooled to room temperature The insoluble material was filtered off washed with water (500 ml) and toluene (500 ml) The filtrate was partitioned in a separatory funnel The organic layer was washed twice with water (1000 ml) dried over anhydrous sodium sulfate filtered The filtrate was concentrated under reduced pressure

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under an argon atmosphere, 4-bromo-3-chlorotoluene (200 g), ethyl 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (376 g), toluene (1000 ml), water (1000 ml), tripotassium phosphate (412 g) and dichlorobis(triphenylphosphine)palladium(II) (14 g) were added to a reaction vessel and the mixture was stirred at 110° C. for 2 hr. The reaction mixture was cooled to room temperature. The insoluble material was filtered off, and washed with water (500 ml) and toluene (500 ml). The filtrate was partitioned in a separatory funnel. The organic layer was washed twice with water (1000 ml), dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure to give the title compound (337 g). The obtained residue was directly used for the next reaction without further purification. The reaction mixture was cooled to room temperature The insoluble material was filtered off washed with water (500 ml) and toluene (500 ml) The filtrate was partitioned in a separatory funnel The organic layer was washed twice with water (1000 ml) dried over anhydrous sodium sulfate filtered The filtrate was concentrated under reduced pressure

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 4-bromo-3-chlorotoluene (4.97 g, 24.2 mmol) in DMF (25 mL) is added Pd(OAc)2 (0.54 g, 2.42 mmol), 1,3-bis(diphenylphosphino)propane (0.998 g, 2.42 mmol), triethylamine (12.5 mL) and methanol (12.5 mL). The reaction vessel is evacuated and purged three times with carbon monoxide gas. A balloon filled with carbon monoxide gas is used to maintain the carbon monoxide atmosphere. The reaction mixture is heated at 80° C. for 8 hr. After cooling H2O (50 mL) is added. The mixture is extracted with hexanes (2×50 mL). The combined organic layers are dried over Na2SO4, filtered, concentrated and chromatographed with 0–3% EtOAc in hexanes. 1.24 g (28%) of methyl 2-chloro-4-methylbenzoate is isolated as a colorless oil. EIMS m/e 184 (M+; 35Cl) and 186 (M+; 37Cl). The reaction vessel is evacuated purged three times with carbon monoxide gas A balloon filled with carbon monoxide gas to maintain the carbon monoxide atmosphere After cooling H2O (50 mL) is added The mixture is extracted with hexanes (2×50 mL) The combined organic layers are dried over Na2SO4 filtered concentrated chromatographed with 0–3% EtOAc in hexanes

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 4-bromo-3-chlorotoluene (4.97 g, 24.2 mmol) in DMF (25 mL) is added Pd(OAc)2 (0.54 g, 2.42 mmol), 1,3-bis(diphenylphosphino)propane (0.998 g, 2.42 mmol), triethylamine (12.5 mL) and methanol (12.5 mL). The reaction vessel is evacuated and purged three times with carbon monoxide gas. A balloon filled with carbon monoxide gas is used to maintain the carbon monoxide atmosphere. The reaction mixture is heated at 80° C. for 8 hr. After cooling H2O (50 mL) is added. The mixture is extracted with hexanes (2×50 mL). The combined organic layers are dried over Na2SO4, filtered, concentrated and chromatographed with 0–3% EtOAc in hexanes. 1.24 g (28%) of methyl 2-chloro-4-methylbenzoate is isolated as a colorless oil. EIMS m/e 184 (M+; 35Cl) and 186 (M+; 37Cl). The reaction vessel is evacuated purged three times with carbon monoxide gas A balloon filled with carbon monoxide gas to maintain the carbon monoxide atmosphere After cooling H2O (50 mL) is added The mixture is extracted with hexanes (2×50 mL) The combined organic layers are dried over Na2SO4 filtered concentrated chromatographed with 0–3% EtOAc in hexanes

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 4-bromo-3-chlorotoluene (4.97 g, 24.2 mmol) in dimethylformamide (25 mL) is added palladium acetate (0.54 g, 2.42 mmol), 1,3-bis(diphenylphosphino)propane (0.998 g, 2.42 mmol), triethylamine (12.5 mL) and methanol (12.5 mL). The reaction vessel is evacuated and purged three times with carbon monoxide gas. A balloon filled with carbon monoxide gas is used to maintain the carbon monoxide atmosphere. The reaction mixture is heated at 80° C. for 8 hr. The mixture is washed with water and extracted with hexanes (2×50 mL). The combined organic layers are dried over sodium sulfate, filtered, concentrated, and chromatographed with 0–3% ethyl acetate in hexanes. 1.24 g (28%) of methyl 2-chloro-4-methylbenzoate is isolated as a colorless oil. The reaction vessel is evacuated purged three times with carbon monoxide gas A balloon filled with carbon monoxide gas to maintain the carbon monoxide atmosphere The mixture is washed with water extracted with hexanes (2×50 mL) The combined organic layers are dried over sodium sulfate filtered concentrated chromatographed with 0–3% ethyl acetate in hexanes

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

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 4-bromo-3-chlorotoluene (4.97 g, 24.2 mmol) in dimethylformamide (25 mL) is added palladium acetate (0.54 g, 2.42 mmol), 1,3-bis(diphenylphosphino)propane (0.998 g, 2.42 mmol), triethylamine (12.5 mL) and methanol (12.5 mL). The reaction vessel is evacuated and purged three times with carbon monoxide gas. A balloon filled with carbon monoxide gas is used to maintain the carbon monoxide atmosphere. The reaction mixture is heated at 80° C. for 8 hr. The mixture is washed with water and extracted with hexanes (2×50 mL). The combined organic layers are dried over sodium sulfate, filtered, concentrated, and chromatographed with 0–3% ethyl acetate in hexanes. 1.24 g (28%) of methyl 2-chloro-4-methylbenzoate is isolated as a colorless oil. The reaction vessel is evacuated purged three times with carbon monoxide gas A balloon filled with carbon monoxide gas to maintain the carbon monoxide atmosphere The mixture is washed with water extracted with hexanes (2×50 mL) The combined organic layers are dried over sodium sulfate filtered concentrated chromatographed with 0–3% ethyl acetate in hexanes