2,5-Dibenzyltetrahydropyrrolo[3,4-c]pyrrole-1,3(2H,3aH)-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:

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

Procedure: 1-Chloroethylchloroformate (3.24 mL) was added dropwise to a solution of compound 1 (5.22 g) in dichloromethane (75 mL) at 0° C. The solution was then heated to reflux for 3 hours, cooled to room temperature and concentrated in vacuo. The residue was then dissolved in methanol (75 mL) and heated to reflux for another 3 hours. The mixture was cooled to 0° C. and ether (200 mL) was added. Filtration afforded the title compound 2 as a white solid (3.38 g, 90%). LCMS: Rf: 0.380 min, M+H+: 231. The solution was then heated to reflux for 3 hours concentrated in vacuo The residue was then dissolved in methanol (75 mL) heated to reflux for another 3 hours The mixture was cooled to 0° C. ether (200 mL) was added Filtration

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

Procedure: A mixture of paraformaldehyde (3.37 g), N-benzylmaleimide (2.80 g) and N-benzylglycine hydrochloride (3.02 g) in toluene (100 mL) was heated to reflux with azeotropic removal of water for 16 hours. The mixture was cooled to room temperature, filtered and concentrated in vacuo. The residue was purified by flash chromatography (20% EtOAc/hexane) to afford the title compound 1 as a low melting white solid (3.60 g, 75%). LCMS: Rf: 2.616 min, M+H+: 321. was heated filtered concentrated in vacuo The residue was purified by flash chromatography (20% EtOAc/hexane)

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

Procedure: 1-Chloroethylchloroformate (3.24 mL) was added dropwise to a solution of compound 1 (5.22 g) in dichloromethane (75 mL) at 0° C. The solution was then heated to reflux for 3 hours, cooled to room temperature and concentrated in vacuo. The residue was then dissolved in methanol (75 mL) and heated to reflux for another 3 hours. The mixture was cooled to 0° C. and ether (200 mL) was added. Filtration afforded the title compound 2 as a white solid (3.38 g, 90%). LCMS: Rf: 0.380 min, M+H+: 231. The solution was then heated to reflux for 3 hours concentrated in vacuo The residue was then dissolved in methanol (75 mL) heated to reflux for another 3 hours The mixture was cooled to 0° C. ether (200 mL) was added Filtration

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

Procedure: A mixture of paraformaldehyde (3.37 g), N-benzylmaleimide (2.80 g) and N-benzylglycine hydrochloride (3.02 g) in toluene (100 mL) was heated to reflux with azeotropic removal of water for 16 hours. The mixture was cooled to room temperature, filtered and concentrated in vacuo. The residue was purified by flash chromatography (20% EtOAc/hexane) to afford the title compound 1 as a low melting white solid (3.60 g, 75%). LCMS: Rf: 2.616 min, M+H+: 321. was heated filtered concentrated in vacuo The residue was purified by flash chromatography (20% EtOAc/hexane)

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

Procedure: N-Benzylmaleimide (5.0 g, 26.7 mmol), and N-(methoxymethyl)-N-(trimethylsilylmethyl) benzylamine (7.0 g, 29.4 mmol) were dissolved in toluene (150 mL). Trifluoroacetic acid (500 μL, 6.5 mmol) was added at room temperature. The reaction was allowed to stir for two hours at room temperature, and the precipitate was filtered off (˜440 mg). The filtrate was concentrated and purified by silica gel column chromatography (20-50% ethyl acetate in hexanes) to afford a white solid (6.2 g, 72%). 1H NMR (400 MHz, CDCl3): δ 7.22-7.05 (m, 8H), 7.01-6.96 (m, 2H), 4.45 (s, 2H), 3.95 (s, 2H), 3.50 (d, J=11.0 Hz), 3.37 (d, J=8.8 Hz), 3.10 (app t, J=9.1 Hz); 13C NMR (400 MHz, CDCl3): δ 175.8 (C═O), 134.8 (Ph), 130.6 (Ph), 129.6 (Ph), 129.3 (Ph), 128.8 (Ph), 128.6 (Ph), 128.3 (Ph), 127.7 (Ph), 57.3 (CH2), 54.0 (CH2), 42.9 (CH), 42.6 (CH2). the precipitate was filtered off (˜440 mg) The filtrate was concentrated purified by silica gel column chromatography (20-50% ethyl acetate in hexanes)