3-METHOXY-1H-PYRROLE-2,5-DIONE

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

实验步骤: To a solution of 3-methoxy-1H-pyrrole-2,5-dione (3 g, 24 mmol) and TFA (0.34 g, 3 mmol) in CH2Cl2 (300 mL) was added slowly a solution of N-(methoxymethyl)-N-(trimethylsilylmethyl)benzylamine (14.2 g, 48 mmol) in CH2Cl2 (100 mL) at a rate such to maintain the internal reaction temperature <2° C. The resulting solution was slowly warmed to ambient temperature and stirred overnight. TLC (petroleum ether/EtOAc=1/1) showed the reaction was complete. The combined five batches of reaction mixture was diluted with saturated sodium bicarbonate (100 mL), and the organics was dried over MgSO4, concentrated and purified by column chromatography (from petroleum ether/EtOAc=10/1 to petroleum ether/EtOAc=1/1) to afford title product (18 g, for 5 batches, 58% yield) as a light yellow oil, which was further purified by preparative HPLC to afford pure title product (4.5 g, 14.6% yield) as an oil. to maintain the internal reaction temperature <2° C five batches of reaction mixture the organics was dried over MgSO4 concentrated purified by column chromatography (from petroleum ether/EtOAc=10/1 to petroleum ether/EtOAc=1/1)

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

实验步骤: To a solution of 3,3-dimethoxypyrrolidine-2,5-dione (12.3 g, 77 mmol) in toluene (500 mL) was added TsOH·water (1.46 g, 7.7 mmol). A Dean Stark Trap was attached and the reaction mixture was refluxed overnight. TLC (petroleum ether/EtOAc=1/1) showed the reaction was complete. The mixture was concentrated and purified by column chromatography (from petroleum ether/EtOAc=2/1 to petroleum ether/EtOAc=1/1) to afford 3-methoxy-1H-pyrrole-2,5-dione (6.9 g, 70% yield) as an orange solid. the reaction mixture was refluxed overnight The mixture was concentrated purified by column chromatography (from petroleum ether/EtOAc=2/1 to petroleum ether/EtOAc=1/1)

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

实验步骤: To a solution of 3,3-dimethoxypyrrolidine-2,5-dione (12.3 g, 77 mmol) in toluene (500 mL) was added TsOH·water (1.46 g, 7.7 mmol). A Dean Stark Trap was attached and the reaction mixture was refluxed overnight. TLC (petroleum ether/EtOAc=1/1) showed the reaction was complete. The mixture was concentrated and purified by column chromatography (from petroleum ether/EtOAc=2/1 to petroleum ether/EtOAc=1/1) to afford 3-methoxy-1H-pyrrole-2,5-dione (6.9 g, 70% yield) as an orange solid. the reaction mixture was refluxed overnight The mixture was concentrated purified by column chromatography (from petroleum ether/EtOAc=2/1 to petroleum ether/EtOAc=1/1)

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

实验步骤: To a 0° C. solution of 3-methoxy-1H-pyrrole-2,5-dione ({see M. Couturier, J. L. Tucker, B. M. Andresen, P. Dube, J. T. Negri, Org. Lett., 2001, 3, 465-467}, 950 mg, 7.47 mmol) and TFA (0.070 mL, 0.897 mmol) in DCM (70 mL) was added slowly a solution of N-benzyl-1-methoxy-N-[(trimethylsilyl)methyl]methanamine (3.06 mL, 12.0 mmol) in DCM (30 mL) at a rate such to maintain the internal reaction temperature <2° C. The resulting bright yellow solution was slowly warmed to ambient temperature and stirred for 18 hrs. The reaction mixture was then cooled to 0° C. and a solution of N-benzyl-1-methoxy-N-[(trimethylsilyl)methyl]methanamine (0.956 mL, 3.74 mmol) in DCM (1 mL) was added dropwise and was warmed to rt and stirred for 3 hrs. The reaction mixture was diluted with saturated sodium bicarbonate (25 mL), the layers were separated and the organic solution was dried (magnesium sulfate), filtered and concentrated under reduced pressure, giving a thick, yellow oil. The crude residue was purified by column chromatography eluting with 5%-50% EtOAc/heptane and again with 0%-25% EtOAc/Heptane to afford the titled compound (1.19 g, 61% yield, 70% purity) as a clear oil that was carried forward to the next step without further purification. to maintain the internal reaction temperature <2° C The reaction mixture was then cooled to 0° C. was warmed to rt stirred for 3 hrs the layers were separated the organic solution was dried (magnesium sulfate) filtered concentrated under reduced pressure giving a thick, yellow oil The crude residue was purified by column chromatography eluting with 5%-50% EtOAc/heptane and again with 0%-25% EtOAc/Heptane

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

实验步骤: To a solution of 3-methoxy-1H-pyrrole-2,5-dione (3 g, 24 mmol) and TFA (0.34 g, 3 mmol) in CH2Cl2 (300 mL) was added slowly a solution of N-(methoxymethyl)-N-(trimethylsilylmethyl)benzylamine (14.2 g, 48 mmol) in CH2Cl2 (100 mL) at a rate such to maintain the internal reaction temperature <2° C. The resulting solution was slowly warmed to ambient temperature and stirred overnight. TLC (petroleum ether/EtOAc=1/1) showed the reaction was complete. The combined five batches of reaction mixture was diluted with saturated sodium bicarbonate (100 mL), and the organics was dried over MgSO4, concentrated and purified by column chromatography (from petroleum ether/EtOAc=10/1 to petroleum ether/EtOAc=1/1) to afford title product (18 g, for 5 batches, 58% yield) as a light yellow oil, which was further purified by preparative HPLC to afford pure title product (4.5 g, 14.6% yield) as an oil. to maintain the internal reaction temperature <2° C five batches of reaction mixture the organics was dried over MgSO4 concentrated purified by column chromatography (from petroleum ether/EtOAc=10/1 to petroleum ether/EtOAc=1/1)

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

实验步骤: To a solution of 3,3-dimethoxypyrrolidine-2,5-dione (12.3 g, 77 mmol) in toluene (500 mL) was added TsOH·water (1.46 g, 7.7 mmol). A Dean Stark Trap was attached and the reaction mixture was refluxed overnight. TLC (petroleum ether/EtOAc=1/1) showed the reaction was complete. The mixture was concentrated and purified by column chromatography (from petroleum ether/EtOAc=2/1 to petroleum ether/EtOAc=1/1) to afford 3-methoxy-1H-pyrrole-2,5-dione (6.9 g, 70% yield) as an orange solid. the reaction mixture was refluxed overnight The mixture was concentrated purified by column chromatography (from petroleum ether/EtOAc=2/1 to petroleum ether/EtOAc=1/1)

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

实验步骤: To a 0° C. solution of 3-methoxy-1H-pyrrole-2,5-dione ({see M. Couturier, J. L. Tucker, B. M. Andresen, P. Dube, J. T. Negri, Org. Lett., 2001, 3, 465-467}, 950 mg, 7.47 mmol) and TFA (0.070 mL, 0.897 mmol) in DCM (70 mL) was added slowly a solution of N-benzyl-1-methoxy-N-[(trimethylsilyl)methyl]methanamine (3.06 mL, 12.0 mmol) in DCM (30 mL) at a rate such to maintain the internal reaction temperature <2° C. The resulting bright yellow solution was slowly warmed to ambient temperature and stirred for 18 hrs. The reaction mixture was then cooled to 0° C. and a solution of N-benzyl-1-methoxy-N-[(trimethylsilyl)methyl]methanamine (0.956 mL, 3.74 mmol) in DCM (1 mL) was added dropwise and was warmed to rt and stirred for 3 hrs. The reaction mixture was diluted with saturated sodium bicarbonate (25 mL), the layers were separated and the organic solution was dried (magnesium sulfate), filtered and concentrated under reduced pressure, giving a thick, yellow oil. The crude residue was purified by column chromatography eluting with 5%-50% EtOAc/heptane and again with 0%-25% EtOAc/Heptane to afford the titled compound (1.19 g, 61% yield, 70% purity) as a clear oil that was carried forward to the next step without further purification. to maintain the internal reaction temperature <2° C The reaction mixture was then cooled to 0° C. was warmed to rt stirred for 3 hrs the layers were separated the organic solution was dried (magnesium sulfate) filtered concentrated under reduced pressure giving a thick, yellow oil The crude residue was purified by column chromatography eluting with 5%-50% EtOAc/heptane and again with 0%-25% EtOAc/Heptane