2-(3-oxobutyl)isoindole-1,3-dione

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:

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

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

Procedure: 1.08 g (5.00 mmol) of N-(3-oxobutyl)phthalimide was dissolved in 10 ml of methanol and to the solution was added 0.835 g (10.0 mmol) of O-methylhydroxylamine hydrochloride. To this suspension was added 2 ml of 5N aqueous sodium hydroxide solution, followed by being stirred at room temperature for 16 hours. The reaction mixture was poured into 100 ml of saturated aqueous sodium hydrogencarbonate solution and extracted with chloroform (30 ml×3), and the combined organic layer was dried over magnesium sulfate. Chloroform was distilled off and the residual solids were washed with hexane to give 1.23 g (yield 100%) of the titled compound as white crystals. extracted with chloroform (30 ml×3) the combined organic layer was dried over magnesium sulfate Chloroform was distilled off the residual solids were washed with hexane

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

Procedure: 1.08 g (5.00 mmol) of N-(3-oxobutyl)phthalimide was dissolved in 10 ml of methanol and to the solution was added 0.835 g (10.0 mmol) of O-methylhydroxylamine hydrochloride. To this suspension was added 2 ml of 5N aqueous sodium hydroxide solution, followed by being stirred at room temperature for 16 hours. The reaction mixture was poured into 100 ml of saturated aqueous sodium hydrogencarbonate solution and extracted with chloroform (30 ml×3), and the combined organic layer was dried over magnesium sulfate. Chloroform was distilled off and the residual solids were washed with hexane to give 1.23 g (yield 100%) of the titled compound as white crystals. extracted with chloroform (30 ml×3) the combined organic layer was dried over magnesium sulfate Chloroform was distilled off the residual solids were washed with hexane

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

Procedure: 1.08 g (5.00 mmol) of N-(3-oxobutyl)phthalimide was dissolved in 10 ml of methanol and to the solution was added 0.695 g (10.0 mmol) of hydroxylamine hydrochloride. To this suspension was added 2 ml of 5N aqueous sodium hydroxide solution, followed by being stirred at room temperature for 16 hours. The reaction mixture was poured into 100 ml of saturated aqueous sodium hydrogencarbonate and extracted with chloroform (30 ml×3), and the combined organic layer was dried over magnesium sulfate. Chloroform was distilled off and the residual solids were washed with hexane to give 0.98 g (yield 84%) of the titled compound as colorless crystals. extracted with chloroform (30 ml×3) the combined organic layer was dried over magnesium sulfate Chloroform was distilled off the residual solids were washed with hexane

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

Procedure: 1.08 g (5.00 mmol) of N-(3-oxobutyl)phthalimide was dissolved in 10 ml of methanol and to the solution was added 0.695 g (10.0 mmol) of hydroxylamine hydrochloride. To this suspension was added 2 ml of 5N aqueous sodium hydroxide solution, followed by being stirred at room temperature for 16 hours. The reaction mixture was poured into 100 ml of saturated aqueous sodium hydrogencarbonate and extracted with chloroform (30 ml×3), and the combined organic layer was dried over magnesium sulfate. Chloroform was distilled off and the residual solids were washed with hexane to give 0.98 g (yield 84%) of the titled compound as colorless crystals. extracted with chloroform (30 ml×3) the combined organic layer was dried over magnesium sulfate Chloroform was distilled off the residual solids were washed with hexane

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of acetic anhydride (5.0 mL, 53.0 mmol) and 7.7 wt % phosphorus pentoxide in methanesulfonic acid (Eaton's Reagent) (5.0 mL, 4.60 mmol) was added 2-(3-oxobutyl)isoindoline-1,3-dione (1.0 g, 4.60 mmol). The reaction was heated at 70° C. and for 8 h. The reaction was allowed to cool to room temperature and maintained overnight. The reaction was diluted with EtOAc, washed with ice cold water, dried (Na2SO4), filtered and concentrated under vacuum. The residue was purified by silica gel chromatography (Analogix, SF40-115 g, 20-100% EtOAc in hexanes). The pure fractions were combined and evaporated to dryness and triturated with 10% EtOAc in hexanes, filtered and evaporated to dryness to give 2-(2,6-dimethyl-4-oxo-4H-pyran-3-yl)methyl)isoindoline-1,3-dione (290 mg, 1.024 mmol, 22.24% yield) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 7.91-7.74 (m, 4 H), 6.06 (s, 1 H), 4.54 (s, 2 H), 2.43 (s, 3 H), 2.22 (s, 3 H). MS(ES) [M+H]+ 284.0. to cool to room temperature maintained overnight washed with ice cold water dried (Na2SO4) filtered concentrated under vacuum The residue was purified by silica gel chromatography (Analogix evaporated to dryness triturated with 10% EtOAc in hexanes filtered evaporated to dryness

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of acetic anhydride (5.0 mL, 53.0 mmol) and 7.7 wt % phosphorus pentoxide in methanesulfonic acid (Eaton's Reagent) (5.0 mL, 4.60 mmol) was added 2-(3-oxobutyl)isoindoline-1,3-dione (1.0 g, 4.60 mmol). The reaction was heated at 70° C. and for 8 h. The reaction was allowed to cool to room temperature and maintained overnight. The reaction was diluted with EtOAc, washed with ice cold water, dried (Na2SO4), filtered and concentrated under vacuum. The residue was purified by silica gel chromatography (Analogix, SF40-115 g, 20-100% EtOAc in hexanes). The pure fractions were combined and evaporated to dryness and triturated with 10% EtOAc in hexanes, filtered and evaporated to dryness to give 2-(2,6-dimethyl-4-oxo-4H-pyran-3-yl)methyl)isoindoline-1,3-dione (290 mg, 1.024 mmol, 22.24% yield) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 7.91-7.74 (m, 4 H), 6.06 (s, 1 H), 4.54 (s, 2 H), 2.43 (s, 3 H), 2.22 (s, 3 H). MS(ES) [M+H]+ 284.0. to cool to room temperature maintained overnight washed with ice cold water dried (Na2SO4) filtered concentrated under vacuum The residue was purified by silica gel chromatography (Analogix evaporated to dryness triturated with 10% EtOAc in hexanes filtered evaporated to dryness

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

Procedure: Prepare a cold (0° C.) solution of 2-(3-oxobutyl)isoindole-1,3-dione (6.8 g, 31.5 mmol) in methanol (50 mL). Add Br2 (3.2 mL, 63 mmol). Allow the reaction to warm to room temperature and stir for 15 hours. Add 10 M sulfuric acid (26 mL) and stir the mixture for 15 hours. Filter off the solids and dry in vacuo to afford 2-(4-bromo-3-oxobutyl)isoindole-1,3-dione (2.3 g). the reaction stir the mixture for 15 hours Filter off the solids dry in vacuo