2-[3-(2,6-二氯苯氧基)丙基]异吲哚-1,3-二酮

反应条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 2,6-dichlorophenol (2.0 g, 12 mmol), N-(3-bromopropyl)phthalimide (3.29 g, 12 mmol) and potassium carbonate (1.69 g, 12 mmol) in anhydrous N,N-dimethylformamide (40 ml) was stirred at 100° C. for 4 hours under an atmosphere of nitrogen. The mixture was then poured into 200 ml of distilled water to give a white precipitate, which was filtered and washed with distilled water. The solid was dried in a vacuum desiccator to yield 4.17 g of N-[3(2,6-dichlorophenoxy)propyl] phthalimide which was dissolved in absolute ethanol (75 ml) and hydrazine hydrate (3 ml, 73 mmol) was added and the mixture refluxed for one hour. After cooling to room temperature, the precipitate was filtered off and the filtrate was concentrated. The residue was chromatographed on silica gel column and eluted with dichloromethane/methanol/ammonium hydroxide (9:2:0.2) to yield 3.2 g of 3-(2,6-dichorophenoxy)propylamine. to give a white precipitate, which was filtered washed with distilled water The solid was dried in a vacuum desiccator

反应条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 2,6-dichlorophenol (500 mg, 3.07 mmol), tetrabutyl ammonium iodide (227 mg, 0.613 mmol) and 2-(3-bromopropyl)isoindoline-1,3-dione (905 mg, 3.37 mmol) was stirred in THF (5 mL) at rt. Cs2CO3 (1.80 g, 5.52 mmol) was added. The resulting mixture was stirred at 50° C. for 16 h. H2O was added to the reaction mixture and the aqueous layer was extracted with EtOAc. The organic layer was dried over MgSO4, filtered and concentrated. The residue was purified by triturating with Et2O to yield Intermediate 9A (1010 mg, 2.88 mmol, 94% yield) as a white powder. LC-MS (ESI) 365 (M+H), RT=2.23 min (Method B). the aqueous layer was extracted with EtOAc The organic layer was dried over MgSO4 filtered concentrated The residue was purified by triturating with Et2O

反应条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 2,6-dichlorophenol (2.0 g, 12 mmol), N-(3-bromopropyl)phthalimide (3.29 g, 12 mmol) and potassium carbonate (1.69 g, 12 mmol) in anhydrous N,N-dimethylformamide (40 ml) was stirred at 100° C. for 4 hours under an atmosphere of nitrogen. The mixture was then poured into 200 ml of distilled water to give a white precipitate, which was filtered and washed with distilled water. The solid was dried in a vacuum desiccator to yield 4.17 g of N-[3(2,6-dichlorophenoxy)propyl] phthalimide which was dissolved in absolute ethanol (75 ml) and hydrazine hydrate (3 ml, 73 mmol) was added and the mixture refluxed for one hour. After cooling to room temperature, the precipitate was filtered off and the filtrate was concentrated. The residue was chromatographed on silica gel column and eluted with dichloromethane/methanol/ammonium hydroxide (9:2:0.2) to yield 3.2 g of 3-(2,6-dichorophenoxy)propylamine. to give a white precipitate, which was filtered washed with distilled water The solid was dried in a vacuum desiccator