1-Benzylpyrrolidine-2,5-dione

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 9.5 g N-Benzylsuccinimide is added to 120 ml THF and the mixture is then cooled to −78° C. A solution of 4-methylbiphenylmagnesium chloride in THF (1.3 eq) is then added. The subsequent mixture is then stirred for 2 h at −78° C. The mixture is then warmed to 10° C. and 100 ml saturated ammonium chloride solution is added. The phases are separated and the aqueous phase is extracted with toluene. The combined organic phases are washed with water then brine and then concentrated in vacuo. The crude material is crystallized from toluene to give 1-Benzyl-5-biphenyl-4-ylmethyl-5-hydroxy-pyrrolidin-2-one. 1H NMR (DMSO): 1.72 (1H), 1.91 (1H), 2.27 (2H), 2.72 (1H), 2.97 (2H), 4.40 (1H), 4.55 (1H), 7.21-7.66 (14H). The mixture is then warmed to 10° C. The phases are separated the aqueous phase is extracted with toluene The combined organic phases are washed with water brine and then concentrated in vacuo The crude material is crystallized from toluene

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 9.5 g N-Benzylsuccinimide is added to 120 ml THF and the mixture is then cooled to −78° C. A solution of 4-methylbiphenylmagnesium chloride in THF (1.3 eq) is then added. The subsequent mixture is then stirred for 2 h at −78° C. The mixture is then warmed to 10° C. and 100 ml saturated ammonium chloride solution is added. The phases are separated and the aqueous phase is extracted with toluene. The combined organic phases are washed with water then brine and then concentrated in vacuo. The crude material is crystallized from toluene to give 1-Benzyl-5-biphenyl-4-ylmethyl-5-hydroxy-pyrrolidin-2-one. 1H NMR (DMSO): 1.72 (1H), 1.91 (1H), 2.27 (2H), 2.72 (1H), 2.97 (2H), 4.40 (1H), 4.55 (1H), 7.21-7.66 (14H). The mixture is then warmed to 10° C. The phases are separated the aqueous phase is extracted with toluene The combined organic phases are washed with water brine and then concentrated in vacuo The crude material is crystallized from toluene

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 9.5 g N-Benzylsuccinimide is added to 120 ml THF and the mixture is then cooled to −78° C. A solution of 4-methylbiphenylmagnesium chloride in THF (1.3 eq) is then added. The subsequent mixture is then stirred for 2 h at −78° C. The mixture is then warmed to 10° C. and 100 ml saturated ammonium chloride solution is added. The phases are separated and the aqueous phase is extracted with toluene. The combined organic phases are washed with water then brine and then concentrated in vacuo. The crude material is crystallized from toluene to give 1-Benzyl-5-biphenyl-4-ylmethyl-5-hydroxy-pyrrolidin-2-one. 1H NMR (DMSO): 1.72 (1H), 1.91 (1H), 2.27 (2H), 2.72 (1H), 2.97 (2H), 4.40 (1H), 4.55 (1H), 7.21-7.66 (14H). The mixture is then warmed to 10° C. The phases are separated the aqueous phase is extracted with toluene The combined organic phases are washed with water brine and then concentrated in vacuo The crude material is crystallized from toluene

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 9.5 g N-Benzylsuccinimide is added to 120 ml THF and the mixture is then cooled to −78° C. A solution of 4-methylbiphenylmagnesium chloride in THF (1.3 eq) is then added. The subsequent mixture is then stirred for 2 h at −78° C. The mixture is then warmed to 10° C. and 100 ml saturated ammonium chloride solution is added. The phases are separated and the aqueous phase is extracted with toluene. The combined organic phases are washed with water then brine and then concentrated in vacuo. The crude material is crystallized from toluene to give 1-Benzyl-5-biphenyl-4-ylmethyl-5-hydroxy-pyrrolidin-2-one. 1H NMR (DMSO): 1.72 (1H), 1.91 (1H), 2.27 (2H), 2.72 (1H), 2.97 (2H), 4.40 (1H), 4.55 (1H), 7.21-7.66 (14H). The mixture is then warmed to 10° C. The phases are separated the aqueous phase is extracted with toluene The combined organic phases are washed with water brine and then concentrated in vacuo The crude material is crystallized from toluene

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 1-(phenylmethyl)-2,5-pyrrolidinedione (1 g, 5.29 mmol) in THF (50 mL) at −78° C. was added cyclopropylmagnesium bromide (42.3 mL, 21.1 mmol) dropwise. The reaction mixture was allowed to warm to 0° C. and stirred for an additional 2 hours. The reaction was quenched with a saturated aqueous solution of ammonium chloride and transferred to a separatory funnel. EtOAc was added, and the organic phase was separated. The aqueous layer was further extracted with EtOAc, and the combined organic layers were washed with brine, dried (MgSO4), filtered and concentrated. Flash chromatography on SiO2 (gradient: 100% hexanes to 80% EtOAc/hexanes) afforded the title compound (400 mg, 33%) as a yellow solid. LC-MS (ES) m/z=232 [M+H]+. The reaction was quenched with a saturated aqueous solution of ammonium chloride transferred to a separatory funnel EtOAc was added the organic phase was separated The aqueous layer was further extracted with EtOAc the combined organic layers were washed with brine dried (MgSO4) filtered concentrated

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 1-(phenylmethyl)-2,5-pyrrolidinedione (1 g, 5.29 mmol) in THF (50 mL) at −78° C. was added cyclopropylmagnesium bromide (42.3 mL, 21.1 mmol) dropwise. The reaction mixture was allowed to warm to 0° C. and stirred for an additional 2 hours. The reaction was quenched with a saturated aqueous solution of ammonium chloride and transferred to a separatory funnel. EtOAc was added, and the organic phase was separated. The aqueous layer was further extracted with EtOAc, and the combined organic layers were washed with brine, dried (MgSO4), filtered and concentrated. Flash chromatography on SiO2 (gradient: 100% hexanes to 80% EtOAc/hexanes) afforded the title compound (400 mg, 33%) as a yellow solid. LC-MS (ES) m/z=232 [M+H]+. The reaction was quenched with a saturated aqueous solution of ammonium chloride transferred to a separatory funnel EtOAc was added the organic phase was separated The aqueous layer was further extracted with EtOAc the combined organic layers were washed with brine dried (MgSO4) filtered concentrated

Conditions: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 2,5-pyrrolidinedione (2.5 g, 25.2 mmol) in DMF (50 mL) was added K2CO3 (4.18 g, 30.3 mmol) followed by benzyl bromide (3.00 mL, 25.2 mmol), and the reaction mixture was stirred overnight at 55° C. Water was added to the reaction mixture (˜200 mL) and a precipitate was immediately observed. The precipitate was filtered, and the white solid was washed with water and dried to afford the title compound (2.7 g, 57%). 1H NMR (400 MHz, CDCl3): δ 2.73 (s, 4H), 4.68 (s, 2H), 7.28-7.37 (m, 3H), 7.39-7.44 (m, 2H). The precipitate was filtered the white solid was washed with water dried

Conditions: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 2,5-pyrrolidinedione (2.5 g, 25.2 mmol) in DMF (50 mL) was added K2CO3 (4.18 g, 30.3 mmol) followed by benzyl bromide (3.00 mL, 25.2 mmol), and the reaction mixture was stirred overnight at 55° C. Water was added to the reaction mixture (˜200 mL) and a precipitate was immediately observed. The precipitate was filtered, and the white solid was washed with water and dried to afford the title compound (2.7 g, 57%). 1H NMR (400 MHz, CDCl3): δ 2.73 (s, 4H), 4.68 (s, 2H), 7.28-7.37 (m, 3H), 7.39-7.44 (m, 2H). The precipitate was filtered the white solid was washed with water dried

Conditions: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 2,5-pyrrolidinedione (2.5 g, 25.2 mmol) in DMF (50 mL) was added K2CO3 (4.18 g, 30.3 mmol) followed by benzyl bromide (3.00 mL, 25.2 mmol), and the reaction mixture was stirred overnight at 55° C. Water was added to the reaction mixture (˜200 mL) and a precipitate was immediately observed. The precipitate was filtered, and the white solid was washed with water and dried to afford the title compound (2.7 g, 57%). 1H NMR (400 MHz, CDCl3): δ 2.73 (s, 4H), 4.68 (s, 2H), 7.28-7.37 (m, 3H), 7.39-7.44 (m, 2H). The precipitate was filtered the white solid was washed with water dried

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 9.5 g N-Benzylsuccinimide is added to 120 ml THF and the mixture is then cooled to −78° C. A solution of 4-methylbiphenylmagnesium chloride in THF (1.3 eq) is then added. The subsequent mixture is then stirred for 2 h at −78° C. The mixture is then warmed to 10° C. and 100 ml saturated ammonium chloride solution is added. The phases are separated and the aqueous phase is extracted with toluene. The combined organic phases are washed with water then brine and then concentrated in vacuo. The crude material is crystallized from toluene to give 1-Benzyl-5-biphenyl-4-ylmethyl-5-hydroxy-pyrrolidin-2-one. 1H NMR (DMSO): 1.72 (1H), 1.91 (1H), 2.27 (2H), 2.72 (1H), 2.97 (2H), 4.40 (1H), 4.55 (1H), 7.21-7.66 (14H). The mixture is then warmed to 10° C. The phases are separated the aqueous phase is extracted with toluene The combined organic phases are washed with water brine and then concentrated in vacuo The crude material is crystallized from toluene

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: N-benzylsuccinimide (0.38 g, 2.0 mmol), triethoxysilane (1.85 mL, 10 mmol), and titanium (IV) isopropoxide (0.06 mL, 0.2 mmol) were dissolved in C6H6 (4.0 mL) and the mixture was heated to 60 ° C. for 16 hours. The solvent was removed in vacuo and the reaction mixture was poured into a mixture of 1 M NaOH (10 mL) and THF (10 mL). This mixture was stirred for 1 hour, poured into ethyl ether (75 mL), and washed with 1 M NaOH (5×50 mL). The ether layer was dried over MgSO4, filtered, and the solvent was removed in vacuo to produce 0.29 g (91% yield) of N-benzylpyrrole as a yellow oil. The solvent was removed in vacuo the reaction mixture was poured into a mixture of 1 M NaOH (10 mL) and THF (10 mL) poured into ethyl ether (75 mL) washed with 1 M NaOH (5×50 mL) The ether layer was dried over MgSO4 filtered the solvent was removed in vacuo

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 9.5 g N-Benzylsuccinimide is added to 120 ml THF and the mixture is then cooled to −78° C. A solution of 4-methylbiphenylmagnesium chloride in THF (1.3 eq) is then added. The subsequent mixture is then stirred for 2 h at −78° C. The mixture is then warmed to 10° C. and 100 ml saturated ammonium chloride solution is added. The phases are separated and the aqueous phase is extracted with toluene. The combined organic phases are washed with water then brine and then concentrated in vacuo. The crude material is crystallized from toluene to give 1-Benzyl-5-biphenyl-4-ylmethyl-5-hydroxy-pyrrolidin-2-one. 1H NMR (DMSO): 1.72 (1H), 1.91 (1H), 2.27 (2H), 2.72 (1H), 2.97 (2H), 4.40 (1H), 4.55 (1H), 7.21-7.66 (14H). The mixture is then warmed to 10° C. The phases are separated the aqueous phase is extracted with toluene The combined organic phases are washed with water brine and then concentrated in vacuo The crude material is crystallized from toluene