2-prop-2-enoxyisoindole-1,3-dione

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

Procedure: To a cooled solution (5 to 10° C.) of N-hydroxyphthalimide (53.80 g, 0.33 mol) in DMF (120 mL), was added DBU (46.36 mL, 0.31 mol) was added in one portion, with stirring. After 10 minutes, allyl bromide (25.96 mL, 0.30 mol) was added in portions. The cooling bath was removed and the reaction mixture was stirred at room temperature for 1 hour, until the color turned from dark burgundy to yellow. Ethyl acetate (300 mL) and water (150 mL) were added, the aqueous phase was separated, and the organic phase was washed with water (4×50 mL). The combined aqueous extracts were back-extracted with EtOAc (3×50 mL) and the total EtOAc solution was washed with saturated NaHCO3 (10×50 mL) until the aqueous phase was pale yellow, then with brine (2×75 mL) and dried over anhydrous MgSO4. Removal of the solvent afforded 58.83 g (96% yield) of the product as a white solid. was added in one portion The cooling bath was removed the reaction mixture was stirred at room temperature for 1 hour, until the color Ethyl acetate (300 mL) and water (150 mL) were added the aqueous phase was separated the organic phase was washed with water (4×50 mL) The combined aqueous extracts were back-extracted with EtOAc (3×50 mL) the total EtOAc solution was washed with saturated NaHCO3 (10×50 mL) until the aqueous phase with brine (2×75 mL) and dried over anhydrous MgSO4 Removal of the solvent

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

Procedure: N-Hydroxyphthalimide (48.9 g) was dissolved in DMF (200 ml) and triethylamine (43.9 ml) was added followed by addition of allyl bromide. The reaction mixture was stirred at room temperature for 18 hours and the resulting precipitated material was removed by filtration. The filtrate was concentrated under reduced pressure. The residue was dissolved in dichloromethane and washed with saturated aqueous sodium bicarbonate, 4 M HCl aq. and brine. The organic layer was dried (MgSO4) and evaporated under reduced pressure. The remaining material was crystallised from hexane/EtOAc, affording 2-allyloxy-isoindole-1,3-dione (43.6 g). This allyl intermediate (2.03 g) was dissolved in toluene (5 ml) and nitroethane (825 mg), phenylisocyanate (2.4 ml) and triethylamine (0.02 eq.) was added. The reaction mixture was stirred at room temperature for 48 hours, and the precipitated material was removed by filtration. The filtrate was evaporated onto silica gel and chromatographed (0 to 50% EtOAc/heptane) and gave 2-(3-methyl-4,5-dihydro-isoxazol-5-ylmethoxy)-isoindole-1,3-dione (2.4 g). 13C-NMR (DMSO-d6) δ 162.9, 155.4, 134.7, 128.5, 123.2, 78.0, 76.9, 40.3, 12.4. This phthalimide intermediate (260 mg) was dissolved in methanol (1 ml) and dichloromethane (1 ml) and hydrazine monohydrate (1.0 eq.) was added. The mixture was stirred at room temperature for 20 hours. The formed solid material was removed by filtration. The filtrate was evaporated under reduced pressure and gave the title compound, which was used without further purification. the resulting precipitated material was removed by filtration The filtrate was concentrated under reduced pressure The residue was dissolved in dichloromethane washed with saturated aqueous sodium bicarbonate, 4 M HCl aq. and brine The organic layer was dried (MgSO4) evaporated under reduced pressure The remaining material was crystallised from hexane/EtOAc

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

Procedure: To a cooled solution (5 to 10° C.) of N-hydroxyphthalimide (53.80 g, 0.33 mol) in DMF (120 mL), was added DBU (46.36 mL, 0.31 mol) was added in one portion, with stirring. After 10 minutes, allyl bromide (25.96 mL, 0.30 mol) was added in portions. The cooling bath was removed and the reaction mixture was stirred at room temperature for 1 hour, until the color turned from dark burgundy to yellow. Ethyl acetate (300 mL) and water (150 mL) were added, the aqueous phase was separated, and the organic phase was washed with water (4×50 mL). The combined aqueous extracts were back-extracted with EtOAc (3×50 mL) and the total EtOAc solution was washed with saturated NaHCO3 (10×50 mL) until the aqueous phase was pale yellow, then with brine (2×75 mL) and dried over anhydrous MgSO4. Removal of the solvent afforded 58.83 g (96% yield) of the product as a white solid. was added in one portion The cooling bath was removed the reaction mixture was stirred at room temperature for 1 hour, until the color Ethyl acetate (300 mL) and water (150 mL) were added the aqueous phase was separated the organic phase was washed with water (4×50 mL) The combined aqueous extracts were back-extracted with EtOAc (3×50 mL) the total EtOAc solution was washed with saturated NaHCO3 (10×50 mL) until the aqueous phase with brine (2×75 mL) and dried over anhydrous MgSO4 Removal of the solvent