tert-butyl 6-amino-3-bromo-2-hydroxybenzoate

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Dicyclohexylcarbodiimide (4.14 g) was added to a stirred solution of 6-amino-3-bromo-2-hydroxybenzoic acid (Intermediate 63, 3.88 g) and DMAP (0.102 g) in tert-butanol (20 mL) and THF (150 mL). The mixture was stirred at room temperature for 4 hours. The resultant white precipitate was filtered off and washed with ethyl acetate. The filtrate was concentrated in vacuo and the residue was purified by chromatography on silica, eluting with a mixture of ethyl acetate and cyclohexane, with a gradient of 2.5-15% to give tert-butyl 6-amino-3-bromo-2-hydroxybenzoate (1.16 g) as a yellow solid. The resultant white precipitate was filtered off washed with ethyl acetate The filtrate was concentrated in vacuo the residue was purified by chromatography on silica eluting with a mixture of ethyl acetate and cyclohexane, with a gradient of 2.5-15%

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Dicyclohexylcarbodiimide (4.14 g) was added to a stirred solution of 6-amino-3-bromo-2-hydroxybenzoic acid (Intermediate 63, 3.88 g) and DMAP (0.102 g) in tert-butanol (20 mL) and THF (150 mL). The mixture was stirred at room temperature for 4 hours. The resultant white precipitate was filtered off and washed with ethyl acetate. The filtrate was concentrated in vacuo and the residue was purified by chromatography on silica, eluting with a mixture of ethyl acetate and cyclohexane, with a gradient of 2.5-15% to give tert-butyl 6-amino-3-bromo-2-hydroxybenzoate (1.16 g) as a yellow solid. The resultant white precipitate was filtered off washed with ethyl acetate The filtrate was concentrated in vacuo the residue was purified by chromatography on silica eluting with a mixture of ethyl acetate and cyclohexane, with a gradient of 2.5-15%

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4-Methylbenzenesulfonyl chloride (2.26 g) was added to a solution of tert-butyl 6-amino-3-bromo-2-hydroxybenzoate (Intermediate 51, 2.85 g), DMAP (1.21 g), and triethylamine (1.5 g) in DCM (40 mL) and left at room temperature for 1 hour. The resulting solution was washed with water, filtered through a phase separator and the filtrate was concentrated in vacuo. The residue was purified by chromatography on silica, eluting with a mixture of ethyl acetate and cyclohexane with a gradient of 0-15% to give tert-butyl 6-amino-3-bromo-2-(4-methylbenzenesulfonyloxyl)benzoate (3.51 g) as an off-white solid. The resulting solution was washed with water filtered through a phase separator the filtrate was concentrated in vacuo The residue was purified by chromatography on silica eluting with a mixture of ethyl acetate and cyclohexane with a gradient of 0-15%

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Dicyclohexylcarbodiimide (4.14 g) was added to a stirred solution of 6-amino-3-bromo-2-hydroxybenzoic acid (Intermediate 63, 3.88 g) and DMAP (0.102 g) in tert-butanol (20 mL) and THF (150 mL). The mixture was stirred at room temperature for 4 hours. The resultant white precipitate was filtered off and washed with ethyl acetate. The filtrate was concentrated in vacuo and the residue was purified by chromatography on silica, eluting with a mixture of ethyl acetate and cyclohexane, with a gradient of 2.5-15% to give tert-butyl 6-amino-3-bromo-2-hydroxybenzoate (1.16 g) as a yellow solid. The resultant white precipitate was filtered off washed with ethyl acetate The filtrate was concentrated in vacuo the residue was purified by chromatography on silica eluting with a mixture of ethyl acetate and cyclohexane, with a gradient of 2.5-15%

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of tert-butyl 6-amino-3-bromo-2-hydroxybenzoate (Intermediate 62, 1.16 g), 2-formylfuran-3-boronic acid pinacol ester (1.073 g), tris-(dibenzylideneacetone)dipalladium (0.184 g), tri-tert-butylphosphonium tetrafluoroborate (0.117 g) and cesium carbonate (3.935 g) was suspended in dioxane (40 mL) and water (5 mL). The mixture was de-gassed and flushed with nitrogen then heated at 70° C. for 3 hours. After cooling, the mixture was concentrated in vacuo. The residue was partitioned between water and ethyl acetate and the combined organic layers were dried (MgSO4) and filtered. The filtrate was concentrated in vacuo and the residue was purified by chromatography on silica, eluting with a mixture of ethyl acetate and cyclohexane, with a gradient of 2.5-25% to give tert-butyl 6-amino-3-(2-formylfuran-3-yl)-2-hydroxybenzoate (0.854 g) as a yellow oil. The mixture was de-gassed flushed with nitrogen After cooling the mixture was concentrated in vacuo The residue was partitioned between water and ethyl acetate the combined organic layers were dried (MgSO4) filtered The filtrate was concentrated in vacuo the residue was purified by chromatography on silica eluting with a mixture of ethyl acetate and cyclohexane, with a gradient of 2.5-25%

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Dicyclohexylcarbodiimide (4.14 g) was added to a stirred solution of 6-amino-3-bromo-2-hydroxybenzoic acid (Intermediate 63, 3.88 g) and DMAP (0.102 g) in tert-butanol (20 mL) and THF (150 mL). The mixture was stirred at room temperature for 4 hours. The resultant white precipitate was filtered off and washed with ethyl acetate. The filtrate was concentrated in vacuo and the residue was purified by chromatography on silica, eluting with a mixture of ethyl acetate and cyclohexane, with a gradient of 2.5-15% to give tert-butyl 6-amino-3-bromo-2-hydroxybenzoate (1.16 g) as a yellow solid. The resultant white precipitate was filtered off washed with ethyl acetate The filtrate was concentrated in vacuo the residue was purified by chromatography on silica eluting with a mixture of ethyl acetate and cyclohexane, with a gradient of 2.5-15%

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4-Methylbenzenesulfonyl chloride (2.26 g) was added to a solution of tert-butyl 6-amino-3-bromo-2-hydroxybenzoate (Intermediate 51, 2.85 g), DMAP (1.21 g), and triethylamine (1.5 g) in DCM (40 mL) and left at room temperature for 1 hour. The resulting solution was washed with water, filtered through a phase separator and the filtrate was concentrated in vacuo. The residue was purified by chromatography on silica, eluting with a mixture of ethyl acetate and cyclohexane with a gradient of 0-15% to give tert-butyl 6-amino-3-bromo-2-(4-methylbenzenesulfonyloxyl)benzoate (3.51 g) as an off-white solid. The resulting solution was washed with water filtered through a phase separator the filtrate was concentrated in vacuo The residue was purified by chromatography on silica eluting with a mixture of ethyl acetate and cyclohexane with a gradient of 0-15%