2-(5-phenylpentyl)isoindole-1,3-dione

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

Procedure: To a stirred solution of 24.0 g (0.131 mole) of 1-chloro-5-phenylpentane (Columbia Organics, Camden, S.C.) in 150 mL of dimethylformamide was added 24.3 g (0.131 mole) of potassium phthalimide (Aldrich) and the reaction mixture was heated at reflux under a nitrogen atmosphere for 15 hr. The solvent was evaporated under reduced pressure to heave a viscous, oily residue. The residue was triturated with 200 mL of water and then the mixture was extracted with four 200-mL portions of methylene chloride. The combined methylene chloride extracts were washed with two 200 mL portions of 2N sodium hydroxide solution, twice with 200 mL portions of water and dried over magnesium sulfate. The solvent was evaporated under reduced pressure to give 35.0 g (91%) of title compound as a viscous oil. A sample of this viscous oil was further purified by high pressure liquid chromatography (Waters Associates Prep LC/System 500A, PrepPak® 500 silica gel; ethyl acetate-hexanes, 1:10). Fractions containing title compound were combined and the solvents were evaporated under reduced pressure to give purified title compound as a colorless, viscous oil. the reaction mixture was heated at reflux under a nitrogen atmosphere for 15 hr The solvent was evaporated under reduced pressure The residue was triturated with 200 mL of water the mixture was extracted with four 200-mL portions of methylene chloride The combined methylene chloride extracts were washed with two 200 mL portions of 2N sodium hydroxide solution, twice with 200 mL portions of water dried over magnesium sulfate The solvent was evaporated under reduced pressure

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

Procedure: To a stirred solution of 24.0 g (0.131 mole) of 1-chloro-5-phenylpentane (Columbia Organics, Camden, S.C.) in 150 mL of dimethylformamide was added 24.3 g (0.131 mole) of potassium phthalimide (Aldrich) and the reaction mixture was heated at reflux under a nitrogen atmosphere for 15 hr. The solvent was evaporated under reduced pressure to heave a viscous, oily residue. The residue was triturated with 200 mL of water and then the mixture was extracted with four 200-mL portions of methylene chloride. The combined methylene chloride extracts were washed with two 200 mL portions of 2N sodium hydroxide solution, twice with 200 mL portions of water and dried over magnesium sulfate. The solvent was evaporated under reduced pressure to give 35.0 g (91%) of title compound as a viscous oil. A sample of this viscous oil was further purified by high pressure liquid chromatography (Waters Associates Prep LC/System 500A, PrepPak® 500 silica gel; ethyl acetate-hexanes, 1:10). Fractions containing title compound were combined and the solvents were evaporated under reduced pressure to give purified title compound as a colorless, viscous oil. the reaction mixture was heated at reflux under a nitrogen atmosphere for 15 hr The solvent was evaporated under reduced pressure The residue was triturated with 200 mL of water the mixture was extracted with four 200-mL portions of methylene chloride The combined methylene chloride extracts were washed with two 200 mL portions of 2N sodium hydroxide solution, twice with 200 mL portions of water dried over magnesium sulfate The solvent was evaporated under reduced pressure

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

Procedure: To a stirred solution of 24.0 g (0.131 mole) of 1-chloro-5-phenylpentane (Columbia Organics, Camden, S.C.) in 150 mL of dimethylformamide was added 24.3 g (0.131 mole) of potassium phthalimide (Aldrich) and the reaction mixture was heated at reflux under a nitrogen atmosphere for 15 hr. The solvent was evaporated under reduced pressure to heave a viscous, oily residue. The residue was triturated with 200 mL of water and then the mixture was extracted with four 200-mL portions of methylene chloride. The combined methylene chloride extracts were washed with two 200 mL portions of 2N sodium hydroxide solution, twice with 200 mL portions of water and dried over magnesium sulfate. The solvent was evaporated under reduced pressure to give 35.0 g (91%) of title compound as a viscous oil. A sample of this viscous oil was further purified by high pressure liquid chromatography (Waters Associates Prep LC/System 500A, PrepPak® 500 silica gel; ethyl acetate-hexanes, 1:10). Fractions containing title compound were combined and the solvents were evaporated under reduced pressure to give purified title compound as a colorless, viscous oil. the reaction mixture was heated at reflux under a nitrogen atmosphere for 15 hr The solvent was evaporated under reduced pressure The residue was triturated with 200 mL of water the mixture was extracted with four 200-mL portions of methylene chloride The combined methylene chloride extracts were washed with two 200 mL portions of 2N sodium hydroxide solution, twice with 200 mL portions of water dried over magnesium sulfate The solvent was evaporated under reduced pressure

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

Procedure: Hydrazine monohydrate (0.36 g, 7.2 mmol) was added to a solution of 2-(5-phenylpentyl)isoindoline-1,3-dione (0.68 g, 2.3 mmol) in 25 mL of EtOH. The solution was stirred under reflux for 5 hrs and then cooled to room temperature. The white precipitate was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was dissolved in a 1N solution of NaOH (80 mL) and extracted with chloroform (3×70 mL). The combined organic layers were washed with brine, dried over Na2SO4 and the solvent was removed under reduced pressure. The crude was purified by column chromatography using a Teledyne ISCO apparatus (solid deposition with TEA, eluent: 20% MeOH in dichloromethane with 1% of TEA) to afford the title compound (0.28 g, 73%) as a white solid. 1H NMR (400 MHz, CDCl3): 1.37-1.48 (m, 2H), 1.58-1.72 (m, 4H), 2.57-2.69 (m, 2H), 3.29 (t, J=6.70 Hz, 2H), 7.13-7.24 (m, 3H), 7.26-7.34 (m, 2H). under reflux for 5 hrs The white precipitate was removed by filtration the filtrate was concentrated under reduced pressure The residue was dissolved in a 1N solution of NaOH (80 mL) extracted with chloroform (3×70 mL) The combined organic layers were washed with brine dried over Na2SO4 the solvent was removed under reduced pressure The crude was purified by column chromatography

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

Procedure: 5-Phenylpentan-1-ol (0.50 g, 3 mmol), triphenylphosphine (0.45 g, 3 mmol), and phthalimide (0.80 g, 3 mmol) were vigorously stirred in dry THE (5 mL) while cooling to 0° C. A solution of DEAD (0.62 g, 3 mmol) in 5 mL of dry THF was added dropwise to the cooled mixture. After stirring at room temperature for 12 his, the solvent was removed by reduced pressure. The crude was purified by column chromatography using a Teledyne ISCO apparatus (cyclohexane:EtOAc 90:10) to afford the title compound (0.68 g, 76%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 1.22-1.34 (m, 2H), 1.49-1.69 (m, 4H), 2.52-2.58 (m, 2H), 3.56 (t, J=7.06 Hz, 2H), 7.06-7.27 (m, 5H), 7.75-7.95 (m, 4H). MS (ESI) m/z: 334 [M-H]−. in dry THE (5 mL) the solvent was removed by reduced pressure The crude was purified by column chromatography

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

Procedure: To a stirred solution of 24.0 g (0.131 mole) of 1-chloro-5-phenylpentane (Columbia Organics, Camden, S.C.) in 150 mL of dimethylformamide was added 24.3 g (0.131 mole) of potassium phthalimide (Aldrich) and the reaction mixture was heated at reflux under a nitrogen atmosphere for 15 hr. The solvent was evaporated under reduced pressure to heave a viscous, oily residue. The residue was triturated with 200 mL of water and then the mixture was extracted with four 200-mL portions of methylene chloride. The combined methylene chloride extracts were washed with two 200 mL portions of 2N sodium hydroxide solution, twice with 200 mL portions of water and dried over magnesium sulfate. The solvent was evaporated under reduced pressure to give 35.0 g (91%) of title compound as a viscous oil. A sample of this viscous oil was further purified by high pressure liquid chromatography (Waters Associates Prep LC/System 500A, PrepPak® 500 silica gel; ethyl acetate-hexanes, 1:10). Fractions containing title compound were combined and the solvents were evaporated under reduced pressure to give purified title compound as a colorless, viscous oil. the reaction mixture was heated at reflux under a nitrogen atmosphere for 15 hr The solvent was evaporated under reduced pressure The residue was triturated with 200 mL of water the mixture was extracted with four 200-mL portions of methylene chloride The combined methylene chloride extracts were washed with two 200 mL portions of 2N sodium hydroxide solution, twice with 200 mL portions of water dried over magnesium sulfate The solvent was evaporated under reduced pressure