3,5-dibromo-3H-2-benzofuran-1-one

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: To a suspension of EXAMPLE 1A (5 g, 17.1 mmol) in water (40 mL) was added powdered potassium hydroxide (1.92 g, 34.3 mmol), and the mixture was refluxed for 1 hour. After cooling, potassium bisulfate (2 g) was added, and the mixture extracted with ethyl acetate (150 mL). The organics were concentrated on a rotary evaporator and dried under vacuum to yield the title compound. MS (ESI) m/z 230 (M+H)+. the mixture was refluxed for 1 hour After cooling the mixture extracted with ethyl acetate (150 mL) The organics were concentrated on a rotary evaporator dried under vacuum

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

実験手順: To a suspension of 5-bromoisobenzofuran-1(3H)-one (5 g, 23.5 mmol) in anhydrous carbon tetrachloride (50 mL) was added N-bromosuccinimide (4.18 g, 23.5 mmol) and a catalytic amount of benzoyl peroxide. The reaction mixture was heated under reflux for 2.5 hours. After cooling, the precipitated solid was filtered off, and the filtrate was concentrated on a rotary evaporator. The residual solid was partitioned between methylene chloride and water. The organic phase was washed with brine, and concentrated. The residue was purified by flash chromatography on silica gel eluting with 20% ethyl acetate in hexanes to yield the title compound. MS (ESI) m/z 290 (M+H)+. The reaction mixture was heated under reflux for 2.5 hours After cooling the precipitated solid was filtered off the filtrate was concentrated on a rotary evaporator The residual solid was partitioned between methylene chloride and water The organic phase was washed with brine concentrated The residue was purified by flash chromatography on silica gel eluting with 20% ethyl acetate in hexanes

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

実験手順: 3,5-dibromoisobenzofuran-1(3H)-one (94) (6.2 g, 21.24 mmol) and triphenylphosphine (5.57 g, 21.24 mmol) were heated at reflux in tetrahydrofuran (100 mL) overnight. The reaction was cooled and filtered to afford the desired material as a white solid (7.20 g, 71.5% yield); 1H NMR (400.132 MHz, CDCl3) δ 7.23 (1H, s), 7.59 (1H, d), 7.72-7.67 (7H, m), 7.92-7.84 (9H, m), 10.20 (1H, s); The reaction was cooled filtered

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

実験手順: 3,5-dibromoisobenzofuran-1(3H)-one (94) (6.2 g, 21.24 mmol) and triphenylphosphine (5.57 g, 21.24 mmol) were heated at reflux in tetrahydrofuran (100 mL) overnight. The reaction was cooled and filtered to afford the desired material as a white solid (7.20 g, 71.5% yield); 1H NMR (400.132 MHz, CDCl3) δ 7.23 (1H, s), 7.59 (1H, d), 7.72-7.67 (7H, m), 7.92-7.84 (9H, m), 10.20 (1H, s); The reaction was cooled filtered

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

実験手順: 5-bromoisobenzofuran-1(3H)-one (E)-2,2′-(diazene-1,2-diyl)bis(2-methylpropanenitrile) (0.540 g, 3.29 mmol) and 1-bromopyrrolidine-2,5-dione (5.85 g, 32.86 mmol) were dissolved CCl4 and heated at reflux for 2 hours. The reaction was cooled and filtered, the filtrate was evaporated to afford the desired material, as a yellow solid (6.05 g, 63.1% yield), which was used directly in the next stage. heated at reflux for 2 hours The reaction was cooled filtered the filtrate was evaporated

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The mixture of 3,5-dibromo-3H-isobenzofuran-1-one (B3) (38 g, 130 mmol) in a solution of 10N NaOH (28.6 mL, 286 mmol) and water (240 mL) is heated for 2 h at 80° C. Activated charcoal (2 g) is added and the mixture is refluxed for another 1 hour. Mixture is hot filtered and acidified with 2N methanesulfonic acid (100 mL). The resulting mixture is cooled in an ice-water bath for 1 h. The solid is filtered and washed with water (4×25 mL) and vacuum dried under KOH to yield 4-bromo-2-formyl-benzoic acid (C3) (26.5 g, 89%, mp: 202° C.). Recrystallization: Dissolved 4-bromo-2-formyl-benzoic acid (C3) in hot EtOH (220 mL) and cooled the mixture in an ice-water bath for 4 h. The solid is filtered and rinsed with cold EtOH (3×20 mL). The solid is then vacuum dried over KOH to yield 4-bromo-2-formyl-benzoic acid (16.8 g, 63%, mp: 204-205° C.). the mixture is refluxed for another 1 hour Mixture is hot filtered The resulting mixture is cooled in an ice-water bath for 1 h The solid is filtered washed with water (4×25 mL) and vacuum dried under KOH

反応条件: temp:158.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The mixture of 5-bromo-3H-isobenzofuran-1-one (A3) (51.5 g, 242 mmol) in bromobenzene (100 mL) is heated to 158° C. Bromine (18.8 mL, 363 mmol) is added dropwise to the mixture over 2 h. The mixture is stirred for another 30 min. at 158° C. The bromobenzene is removed by distillation under vacuum. The residue is vacuum dried 1 hour at 120° C. to yield a black crystalline residue. Recrystallization: The residue is dissolved in hot isopropyl ether (300 mL). Activated charcoal (1 g) is added, stirred and filtered while hot. The filtrate is cooled in ice-water bath (0° C.) over night. The solid is filtered and is rinsed with cold isopropyl ether (2×10 mL) and vacuum dry over KOH (KOH) to yield 3,5-dibromo-3H-isobenzofuran-1-one (B3) (38 g, 54%, mp: 100° C.). The bromobenzene is removed by distillation under vacuum dried 1 hour at 120° C. to yield a black crystalline residue Recrystallization The residue is dissolved in hot isopropyl ether (300 mL) Activated charcoal (1 g) is added stirred filtered while hot The filtrate is cooled in ice-water bath (0° C.) over night The solid is filtered is rinsed with cold isopropyl ether (2×10 mL) and vacuum dry over KOH (KOH)

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

実験手順: To a suspension of EXAMPLE 1A (5 g, 17.1 mmol) in water (40 mL) was added powdered potassium hydroxide (1.92 g, 34.3 mmol), and the mixture was refluxed for 1 hour. After cooling, potassium bisulfate (2 g) was added, and the mixture extracted with ethyl acetate (150 mL). The organics were concentrated on a rotary evaporator and dried under vacuum to yield the title compound. MS (ESI) m/z 230 (M+H)+. the mixture was refluxed for 1 hour After cooling the mixture extracted with ethyl acetate (150 mL) The organics were concentrated on a rotary evaporator dried under vacuum