1-bromo-3-chloro-5-methoxybenzene

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

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: 1-Bromo-3-chloro-5-methoxybenzene (Preparation 22, 6.0 g, 27 mmol) and trichloroisocyanuric acid (2.3 g, 9.9 mmol) were stirred in dimethylformamide (100 ml) at 50° C. for 3 hours. N-Heptane was added and the mixture filtered to remove insoluble impurities. The mixture was then concentrated in vacuo and the residue purified by silica gel column chromatography, eluting with 90:10 heptane:ethyl acetate to afford the title compound as a white solid (5.0 g). the mixture filtered to remove insoluble impurities The mixture was then concentrated in vacuo the residue purified by silica gel column chromatography eluting with 90:10 heptane

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

Procedure: To a solution of 1-bromo-3-chloro-5-fluorobenzene (25 g, 120 mmol) in methanol (800 ml) was added sodium methoxide (64 g, 1180 mmol). The reaction was heated to reflux for 9 days. The reaction was then concentrated in vacuo to one fifth of the volume (150 ml), cooled. and water (1000 ml) added. The mixture was extracted with diethyl ether (3×150 ml). The combined organic extracts were washed with brine (2×100 ml), dried over Na2SO4 and evaporated to afford the title compound (24.6 g). The reaction was heated to reflux for 9 days The reaction was then concentrated in vacuo to one fifth of the volume (150 ml) cooled and water (1000 ml) added The mixture was extracted with diethyl ether (3×150 ml) The combined organic extracts were washed with brine (2×100 ml) dried over Na2SO4 evaporated

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

Procedure: Sodium methoxide (4.5M solution in methanol, 2.20 ml, 10.0 mmol) was added dropwise to a stirred solution of 1-fluoro-3-chloro-5-bromobenzene (1.00 g, 4.77 mmol) in methanol (28 ml) at room temperature under a nitrogen atmosphere. The mixture was heated under reflux for 3 days and then cooled to room temperature. The mixture was evaporated under reduced pressure and the resulting yellow oil was dissolved in dichloromethane (30 ml). The dichloromethane solution was washed with water (2×20 ml) dried over magnesium sulphate, filtered and evaporated under reduced pressure. The residue was purified by chromatography on silica gel eluting with cyclohexane to provide the title compound as a colourless oil (302 mg). The mixture was heated under reflux for 3 days The mixture was evaporated under reduced pressure the resulting yellow oil was dissolved in dichloromethane (30 ml) The dichloromethane solution was washed with water (2×20 ml) dried over magnesium sulphate filtered evaporated under reduced pressure The residue was purified by chromatography on silica gel eluting with cyclohexane

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

Procedure: Sodium methoxide (4.5M solution in methanol, 2.20 ml, 10.0 mmol) was added dropwise to a stirred solution of 1-fluoro-3-chloro-5-bromobenzene (1.00 g, 4.77 mmol) in methanol (28 ml) at room temperature under a nitrogen atmosphere. The mixture was heated under reflux for 3 days and then cooled to room temperature. The mixture was evaporated under reduced pressure and the resulting yellow oil was dissolved in dichloromethane (30 ml). The dichloromethane solution was washed with water (2×20 ml) dried over magnesium sulphate, filtered and evaporated under reduced pressure. The residue was purified by chromatography on silica gel eluting with cyclohexane to provide the title compound as a colourless oil (302 mg). The mixture was heated under reflux for 3 days The mixture was evaporated under reduced pressure the resulting yellow oil was dissolved in dichloromethane (30 ml) The dichloromethane solution was washed with water (2×20 ml) dried over magnesium sulphate filtered evaporated under reduced pressure The residue was purified by chromatography on silica gel eluting with cyclohexane

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

Procedure: Sodium methoxide (2.20 ml of a 4.5M solution in methanol, 10.0 mmol) was added dropwise to a stirred solution of 1-fluoro-3-chloro-5-bromobenzene (1.00 g, 4.77 mmol) in methanol (28 ml) at room temperature under nitrogen. The reaction was heated under reflux for 3 days and cooled to room temperature. The mixture was concentrated under reduced pressure and the resulting yellow oil was dissolved in dichloromethane (30 ml). The resulting solution was washed with water (2×20 ml) dried over magnesium sulphate, filtered and concentrated under reduced pressure. The crude product was purified by flash column chromatography on silica gel eluting with cyclohexane to provide the title compound (302 mg) as a colourless oil. The reaction was heated under reflux for 3 days The mixture was concentrated under reduced pressure the resulting yellow oil was dissolved in dichloromethane (30 ml) The resulting solution was washed with water (2×20 ml) dried over magnesium sulphate filtered concentrated under reduced pressure The crude product was purified by flash column chromatography on silica gel eluting with cyclohexane

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

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

Procedure: Sodium methoxide (2.20 ml of a 4.5M solution in methanol, 10.0 mmol) was added dropwise to a stirred solution of 1-fluoro-3-chloro-5-bromobenzene (1.00 g, 4.77 mmol) in methanol (28 ml) at room temperature under nitrogen. The reaction was heated under reflux for 3 days and cooled to room temperature. The mixture was concentrated under reduced pressure and the resulting yellow oil was dissolved in dichloromethane (30 ml). The resulting solution was washed with water (2×20 ml) dried over magnesium sulphate, filtered and concentrated under reduced pressure. The crude product was purified by flash column chromatography on silica gel eluting with cyclohexane to provide the title compound (302 mg) as a colourless oil. The reaction was heated under reflux for 3 days The mixture was concentrated under reduced pressure the resulting yellow oil was dissolved in dichloromethane (30 ml) The resulting solution was washed with water (2×20 ml) dried over magnesium sulphate filtered concentrated under reduced pressure The crude product was purified by flash column chromatography on silica gel eluting with cyclohexane

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

Procedure: Sodium methoxide (2.20 ml of a 4.5M solution in methanol, 10.0 mmol) was added dropwise to a stirred solution of 1-fluoro-3-chloro-5-bromobenzene (1.00 g, 4.77 mmol) in methanol (28 ml) at room temperature under nitrogen. The reaction was heated under reflux for 3 days and cooled to room temperature. The mixture was concentrated under reduced pressure and the resulting yellow oil was dissolved in dichloromethane (30 ml). The resulting solution was washed with water (2×20 ml) dried over magnesium sulphate, filtered and concentrated under reduced pressure. The crude product was purified by flash column chromatography on silica gel eluting with cyclohexane to provide the title compound (302 mg) as a colourless oil. The reaction was heated under reflux for 3 days The mixture was concentrated under reduced pressure the resulting yellow oil was dissolved in dichloromethane (30 ml) The resulting solution was washed with water (2×20 ml) dried over magnesium sulphate filtered concentrated under reduced pressure The crude product was purified by flash column chromatography on silica gel eluting with cyclohexane

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

Procedure: Sodium methoxide (2.20 ml of a 4.5M solution in methanol, 10.0 mmol) was added dropwise to a stirred solution of 1-fluoro-3-chloro-5-bromobenzene (1.00 g, 4.77 mmol) in methanol (28 ml) at room temperature under nitrogen. The reaction was heated under reflux for 3 days and cooled to room temperature. The mixture was concentrated under reduced pressure and the resulting yellow oil was dissolved in dichloromethane (30 ml). The resulting solution was washed with water (2×20 ml) dried over magnesium sulphate, filtered and concentrated under reduced pressure. The crude product was purified by flash column chromatography on silica gel eluting with cyclohexane to provide the title compound (302 mg) as a colourless oil. The reaction was heated under reflux for 3 days The mixture was concentrated under reduced pressure the resulting yellow oil was dissolved in dichloromethane (30 ml) The resulting solution was washed with water (2×20 ml) dried over magnesium sulphate filtered concentrated under reduced pressure The crude product was purified by flash column chromatography on silica gel eluting with cyclohexane