1-(3-bromophenyl)-3,3-dimethylpyrrolidine-2,5-dione

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

Procedure: 1-(3-Bromophenyl)-3,3-dimethyl-pyrrolidine-2,5-dione (10.6 g, 37.7 mmol) was suspended in 200 ml of THF. Borane dimethyl sulfide complex (33 ml of a 10.1 M solution) was added and the reaction was stirred at room temperature for 3 hrs. The reaction was cooled in an ice bath. Methanol (100 ml) was added dropwise, followed by 300 ml of water. This mixture was transferred to a separatory funnel and DCM was added. The organic phase was isolated, washed with brine, filtered through Celite and concentrated. The product was chromatographed using a gradient of 0% to 5% ethyl acetate in hexanes, concentrated, triturated with methanol and filtered to give 8.0 g (84%) of 1-(3-bromophenyl)-3,3-dimethyl-pyrrolidine. The reaction was cooled in an ice bath This mixture was transferred to a separatory funnel The organic phase was isolated washed with brine filtered through Celite concentrated The product was chromatographed concentrated triturated with methanol filtered

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-Bromophenylamine (10.0 g, 58.1 mmol) and 3,3-dimethyl-dihydro-furan-2,5-dione (8.2 g, 63.9 mmol) were suspended in 300 ml DCM. The reaction was stirred at 50° C. for 3 h. The reaction was cooled to room temperature and 1,1′-carbonyldiimidazole (11.3 g, 69.7 mmol) was added in portions. The reaction was heated again to 50° C. and stirred overnight. The solvent was evaporated and the product was crystallized from isopropyl alcohol to give 9.3 g of 1-(3-bromophenyl)-3,3-dimethyl-pyrrolidine-2,5-dione. The mother liquor was concentrated and chromatographed using a gradient of 0% to 20% ethyl acetate in hexanes to give another 1.3 g of product for a combined yield of 10.6 g (65%). The reaction was cooled to room temperature The reaction was heated again to 50° C. stirred overnight The solvent was evaporated the product was crystallized from isopropyl alcohol

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

Procedure: 1-(3-Bromo-phenyl)-3,3-dimethyl-pyrrolidine-2,5-dione (2.5 g, 8.9 mmol) was suspended in 45 ml of THF. Borane (7.9 ml of a 10.1M solution in methyl sulfide) was added and the reaction was stirred at room temperature for 3 hours. The reaction was cooled to 0° C. in an ice bath and 20 ml of methanol was added dropwise, then 60 ml of water. The mixture was transferred to a separatory funnel and methylene chloride was added. The organic phase was washed with water and brine, filtered through celite and concentrated. The crude product was purified by flash chromatography using a gradient of 0% to 5% ethyl acetate in hexanes to give 1.7 g (75%) of 1-(3-bromo-phenyl)-3,3-dimethyl-pyrrolidine. The reaction was cooled to 0° C. in an ice bath The mixture was transferred to a separatory funnel The organic phase was washed with water and brine filtered through celite concentrated The crude product was purified by flash chromatography

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-Bromo-phenylamine (10.0 g, 58.1 mmol) and 3,3-dimethyl-dihydro-furan-2,5-dione (8.2 g, 63.9 mmol) were suspended in 387 ml of methylene chloride and heated at 50° C. for 3 hours. Carbonyldiimidazole (11.3 g, 69.7 mmol) was added in portions and the reaction was heated at 50° C. overnight. Most of the solvent was removed on a rotary evaporator. The solid residue was triturated with 20% ethyl acetate in hexanes, filtered and dried to give 15 g (92%) of somewhat impure 1-(3-bromo-phenyl)-3,3-dimethyl-pyrrolidine-2,5-dione which was used without further purification. the reaction was heated at 50° C. overnight Most of the solvent was removed on a rotary evaporator The solid residue was triturated with 20% ethyl acetate in hexanes filtered dried