methyl 4-amino-3-bromo-5-hydroxybenzoate

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

Procedure: To a mixture of methyl 4-amino-3-bromo-5-hydroxybenzoate (1.0 g, 4.06 mmol), (4-fluorophenyl)-boronic acid (0.85 g, 6.1 mmol), 3,3′,3″-phosphinidynetris (benzensulfonic acid) trisodium salt (195.0 mg, 0.31 mmol), palladium(II) acetate (23.0 mg, 0.10 mmol) and diisopropylamine (0.58 mL, 4.06 mmol) were added N,N-dimethylformamide (15.2 mL) and water (5.1 mL). The mixture was heated to 80° C. After 18 h, the mixture was cooled to ambient temperature and ethyl acetate was added. The organic layer was washed with water (3×), brine, dried over magnesium sulfate, filtered and concentrated. Purification by silica gel chromatography (100% hexanes→50% hexanes/ethyl acetate) gave the title compound (0.27 g). LC-MS [M+1]=262.2. the mixture was cooled to ambient temperature The organic layer was washed with water (3×), brine dried over magnesium sulfate filtered concentrated Purification by silica gel chromatography (100% hexanes→50% hexanes/ethyl acetate)

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

Procedure: To a solution of methyl 4-amino-3-hydroxybenzoate (2.5 g, 15.0 mmol) in dichloromethane (71 mL) and N,N-dimethylformamide (3.6 mL) was added N-bromosuccinamide (2.93 g, 16.5 mmol). The mixture was stirred at ambient temperature. After 15 min, the mixture was quenched with sat. sodium sulfite. Hydrochloric acid (1.0 M) was added and the mixture was extracted with dichloromethane (3×). The combined organic layer was washed with brine, dried over magnesium sulfate, filtered and concentrated. Purification by silica gel chromatography (100% hexanes→100% ethyl acetate) gave the title compound (1.2 g). LC-MS [M]=246.0. the mixture was quenched with sat. sodium sulfite Hydrochloric acid (1.0 M) was added the mixture was extracted with dichloromethane (3×) The combined organic layer was washed with brine dried over magnesium sulfate filtered concentrated Purification by silica gel chromatography (100% hexanes→100% ethyl acetate)

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

Procedure: To a solution of methyl 4-amino-3-hydroxybenzoate (2.5 g, 15.0 mmol) in dichloromethane (71 mL) and N,N-dimethylformamide (3.6 mL) was added N-bromosuccinamide (2.93 g, 16.5 mmol). The mixture was stirred at ambient temperature. After 15 min, the mixture was quenched with sat. sodium sulfite. Hydrochloric acid (1.0 M) was added and the mixture was extracted with dichloromethane (3×). The combined organic layer was washed with brine, dried over magnesium sulfate, filtered and concentrated. Purification by silica gel chromatography (100% hexanes→100% ethyl acetate) gave the title compound (1.2 g). LC-MS [M]=246.0. the mixture was quenched with sat. sodium sulfite Hydrochloric acid (1.0 M) was added the mixture was extracted with dichloromethane (3×) The combined organic layer was washed with brine dried over magnesium sulfate filtered concentrated Purification by silica gel chromatography (100% hexanes→100% ethyl acetate)

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

Procedure: To a mixture of methyl 4-amino-3-bromo-5-hydroxybenzoate (1.0 g, 4.06 mmol), (4-fluorophenyl)-boronic acid (0.85 g, 6.1 mmol), 3,3′,3″-phosphinidynetris (benzensulfonic acid) trisodium salt (195.0 mg, 0.31 mmol), palladium(II) acetate (23.0 mg, 0.10 mmol) and diisopropylamine (0.58 mL, 4.06 mmol) were added N,N-dimethylformamide (15.2 mL) and water (5.1 mL). The mixture was heated to 80° C. After 18 h, the mixture was cooled to ambient temperature and ethyl acetate was added. The organic layer was washed with water (3×), brine, dried over magnesium sulfate, filtered and concentrated. Purification by silica gel chromatography (100% hexanes→50% hexanes/ethyl acetate) gave the title compound (0.27 g). LC-MS [M+1]=262.2. the mixture was cooled to ambient temperature The organic layer was washed with water (3×), brine dried over magnesium sulfate filtered concentrated Purification by silica gel chromatography (100% hexanes→50% hexanes/ethyl acetate)

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

Procedure: To a solution of methyl 4-amino-3-hydroxybenzoate (2.5 g, 15.0 mmol) in dichloromethane (71 mL) and N,N-dimethylformamide (3.6 mL) was added N-bromosuccinamide (2.93 g, 16.5 mmol). The mixture was stirred at ambient temperature. After 15 min, the mixture was quenched with sat. sodium sulfite. Hydrochloric acid (1.0 M) was added and the mixture was extracted with dichloromethane (3×). The combined organic layer was washed with brine, dried over magnesium sulfate, filtered and concentrated. Purification by silica gel chromatography (100% hexanes→100% ethyl acetate) gave the title compound (1.2 g). LC-MS [M]=246.0. the mixture was quenched with sat. sodium sulfite Hydrochloric acid (1.0 M) was added the mixture was extracted with dichloromethane (3×) The combined organic layer was washed with brine dried over magnesium sulfate filtered concentrated Purification by silica gel chromatography (100% hexanes→100% ethyl acetate)