1-benzylpyrrole-2,5-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:; See reaction.notes.procedure_details.

Procedure: A solution of 35 g of 2,5-dimethylbenzophenone and 31.5 g of N-benzylmaleimide in 500 cc of acetone or methylene chloride is irradiated with a mercury high pressure lamp through a pyrex filter, until all the material has reacted (20 to 130 hours), filtration and concentration by evaporation are then effected. After crystallization from ether, the residue yields 35 g of 2-benzyl-3a,4,9,9a-tetrahydro-6-methyl-4-phenyl-benz[f]isoindolin-4-ol-1,3-dione, having a M.P. of 162-164°, which are dissolved in 170 cc of trifluoroacetic acid. The solution is stirred at 25° for 3 hours and concentrated by evaporation. After crystallization from methylene chloride/methanol, the residue yields 30 g of (9aRS)-2-benzyl-9,9a-dihydro-6-methyl-4-phenyl-benz[f]isoindoline-1,3-dione, having a M.P. of 156°-158°. filter, until all the material has reacted (20 to 130 hours), filtration and concentration by evaporation After crystallization from ether

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

Procedure: 850 mg of 2-isopropenyl-1-methylindole and 980 mg of N-benzylmaleimide were stirred at 110° C. for 30 minutes. The resulting solid was recrystallized from 10 ml of ethanol to obtain 1.22 g (yield: 69%) of N-benzyl-1-methyl-9-methyl-1,2,3,4-tetrahydrocarbazole-3,4-dicarboximide as colorless needles. The resulting solid was recrystallized from 10 ml of ethanol

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

Procedure: Ethyl diazoacetate (13 g, 114 mmol) in diethyl ether (100 ml) was added dropwise to a solution of N-benzylmaleimide (10 g, 53 mmol) in diethyl ether (250 ml). The resulting mixture was allowed to stir for 18 hours; the solvent was then removed in vacuo, and the resulting residue partitioned between methylene chloride and water. The organic layer was dried over sodium sulfate, filtered and concentrated to provide the title product as a white solid, mp 145°-146° with decomposition (16 g, 53 mmol, 100% yield). 1H NMR (CDCl3): 7.31 (m, 5H), 7.02 (bs, 1H), 4.89 (dd, J=11, 2 Hz, 1H), 4.65 (s, 2H), 4.55 (d, J=10 Hz, 1H), 4.36 (q, J=7 Hz, 2H), 1.37 (t, J=7 Hz, 3H). the solvent was then removed in vacuo the resulting residue partitioned between methylene chloride and water The organic layer was dried over sodium sulfate filtered concentrated

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

Procedure: 74.8 g (0.4 mol) of N-benzylmaleimide are reacted with 58 g (0.5 mol) of 2-chloroethylamine hydrochloride and 50.5 g (0.5 mol) of triethylamine in accordance with the working instructions of Example Ia. After working up by chromatography, 81.6 g (77% of theory) of an oil with an RF value of 0.24 (on silica gel using ethyl acetate:petroleum ether=1:1) are obtained. are obtained

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

Procedure: 74.8 g (0.4 mol) of N-benzylmaleimide [Arch. Pharm. 308, 489 (1975)] and 52.0 g (0.4 mol) of 2-chloroethyl-methylamine hydrochloride are initially introduced into 400 ml of dioxane and 40.4 g (0.4 mol) of triethylamine are added dropwise at 20° C. The mixture is then boiled under reflux for 5 hours. The batch is subsequently poured into 2 l of ice-water and extracted with 3 portions of 400 ml of chloroform and the extract is washed with water, dried over sodium sulphate and concentrated on a rotary evaporator. Chromatography of the residue (101.1 g) on silica gel using ethyl acetate:petroleum ether (1:2) gives 56.8 g (51% of theory) of an oil. are added dropwise at 20° C under reflux for 5 hours extracted with 3 portions of 400 ml of chloroform the extract is washed with water dried over sodium sulphate concentrated on a rotary evaporator gives 56.8 g (51% of theory) of an oil

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

Procedure: Ethyl diazoacetate (30.3 mL, 288.5 mmol) was added dropwise over a period of 30 min to a solution of N-benzylmaleimide (49.5 g, 264.7 mmol) in diethyl ether (300 mL) and the mixture was stirred for 4 days at room temperature. The resulting precipitate was filtered off, washed with diethyl ether (100 mL) and dried under vacuum to provide title compound as a white solid (72 g, 90%). Method B HPLC-MS: MH+ requires m/z=302. Found: m/z=302, Rt=1.74 min (83%). The resulting precipitate was filtered off washed with diethyl ether (100 mL) dried under vacuum

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

Procedure: Ethyl diazoacetate (13 g, 114 mmol) in diethyl ether (100 ml) was added dropwise to a solution of N-benzylmaleimide (10 g, 53 mmol) in diethyl ether (250 ml). The resulting mixture was allowed to stir for 18 hours; the solvent was then removed in vacuo, and the resulting residue partitioned between methylene chloride and water. The organic layer was dried over sodium sulfate, filtered and concentrated to provide the title product as a white solid, mp 145°-146° with decomposition (16 g, 53 mmol, 100% yield). 1H NMR (CDCl3): 7.31 (m, 5H), 7.02 (bs, 1H), 4.89 (dd, J=11, 2 Hz, 1H), 4.65 (s, 2H), 4.55 (d, J=10 Hz, 1H), 4.36 (q, J=7 Hz, 2H), 1.37 (t, J=7 Hz, 3H). the solvent was then removed in vacuo the resulting residue partitioned between methylene chloride and water The organic layer was dried over sodium sulfate filtered concentrated

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

Procedure: Ethyl diazoacetate (13 g, 114 mmol) in diethyl ether (100 ml) was added dropwise to a solution of N-benzylmaleimide (10 g, 53 mmol) in diethyl ether (250 ml). The resulting mixture was allowed to stir for 18 hours; the solvent was then removed in vacuo, and the resulting residue partitioned between methylene chloride and water. The organic layer was dried over sodium sulfate, filtered and concentrated to provide the title product as a white solid, mp 145°-146° with decomposition (16 g, 53 mmol, 100% yield). 1H NMR (CDCl3): 7.31 (m, 5H), 7.02 (bs, 1H), 4.89 (dd, J=11, 2 Hz, 1H), 4.65 (s, 2H), 4.55 (d, J=10 Hz, 1H), 4.36 (q, J=7 Hz, 2H), 1.37 (t, J=7 Hz, 3H). the solvent was then removed in vacuo the resulting residue partitioned between methylene chloride and water The organic layer was dried over sodium sulfate filtered concentrated

Conditions: temp:-19.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A stirred mixture of 9.4 g of 4A bead molecular sieves, 9.4 g of dry Celite, (trademark), 5.62 g (30 mmol) of N-benzylmaleimide, and 120 mL of dry toluene under nitrogen was cooled to -19° C. and treated with 2.7 mL (3.9 mmol, 1.3 equivalents) of bromonitromethane. Tetrabutylammonium 2,6-di-t-butylphenoxide, the title product of Example 1, 23.38 g, was added, via a solid addition funnel, over 1.75 hours to the stirred reaction mixture at -19° C. After 15 minutes of further stirring, the reaction mixture was warmed to -1° C. and treated with 60 mL of 2N hydrochloric acid with vigorous stirring. The mixture was stirred for 1 hour and filtered through a Celite pad. The filtered solids were washed two times with 100 mL of toluene and the combined toluene solutions were washed two times with 60 mL of 2N hydrochloric acid, two times with 50 mL of water and once with brine. The resulting solution was stirred with 3.0 g of Darco (trademark) KBB overnight and filtered. The recovered Darco was washed two times with 50 mL of toluene, the toluene solutions were combined and the toluene was removed under vacuum to yield 14.95 g of a partially solidified orange-brown oil. This material was dissolved in 30 mL of toluene at 50° C. The toluene was removed by distillation under reduced pressure at 50° C., using a heated oil bath, while maintaining a constant volume by adding a total of 120 mL of isopropanol. This resulting slurry was stirred at 50° C. for 3 hours. Heating of the mixture was discontinued and the mixture was allowed to slowly cool to room temperature overnight. The mixture was then cooled to 0° C. for 3 hours and filtered. The filtered solids were washed with 10 mL of cold isopropanol followed by hexanes, and dried under vacuum giving 3.07 g (42% yield) of the title compound as a light tan solid. the reaction mixture was warmed to -1° C. filtered through a Celite pad The filtered solids were washed two times with 100 mL of toluene the combined toluene solutions were washed two times with 60 mL of 2N hydrochloric acid, two times with 50 mL of water The resulting solution was stirred with 3.0 g of Darco (trademark) KBB overnight filtered The recovered Darco was washed two times with 50 mL of toluene the toluene was removed under vacuum to yield 14.95 g of a partially solidified orange-brown oil The toluene was removed by distillation under reduced pressure at 50° C. while maintaining a constant volume by adding a total of 120 mL of isopropanol This resulting slurry was stirred at 50° C. for 3 hours Heating of the mixture to slowly cool to room temperature overnight The mixture was then cooled to 0° C. for 3 hours filtered The filtered solids were washed with 10 mL of cold isopropanol dried under vacuum

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

Procedure: 74.8 g (0.4 mol) of N-benzylmaleimide are reacted with 58 g (0.5 mol) of 2-chloroethylamine hydrochloride and 50.5 g (0.5 mol) of triethylamine in accordance with the working instructions of Example Ia. After working up by chromatography, 81.6 g (77% of theory) of an oil with an RF value of 0.24 (on silica gel using ethyl acetate: petroleum ether=1:1) are obtained. are obtained