2-(2-phenylethyl)isoindole-1,3-dione

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:177.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1,3-Dioxo-2-(1-phenethyl-2,6-dioxopiperidin-3-yl)isoindoline (8) was specifically prepared and isolated as follows. A mixture of N-phthaloyl-DL-glutamic anhydride (300 mg, 1.13 mmol) and phenethylamine (139 mg, 1.13 mmol) was stirred in a 177° C. oil bath for two hours. The reaction mixture was cooled down and purified by column chromatography, first using petroleum ether/dichloromethane (1:5) as an eluent to afford N-phenethyl phthalimide as a pale yellow solid [1H NMR (CDCl3) δ 7.78-7.77 (m, 2H), 7.65-7.62 (m 2H), 7.22-7.16 (m, 5H), 3.83 (t, 2H), 2.92 (t, 2H)], and then using dichloromethane as an eluent to afford N-phenethyl thalidomide as a syrup that was then recrystallized from ether to provide white crystals [(139 mg, 34%): mp 122-123° C.; 1H NMR (CDCl3) δ 7.84-7.81 (dd, J=3.1 Hz, J=5.4 Hz, 2H), 7.72-7.69 (dd, J=3.1 Hz, J=5.4 Hz, 2H), 7.20-7.14 (m, 5H), 4.89 (dd, J=5.4 Hz, J=12.5 Hz, 1H), 4.01-3.92 (m, 2H), 2.90-2.63 (m, 5H), 2.06-2.02 (m, 1H); Anal. Calcd for C21H18N2O4: C, 69.60; H, 5.01; N, 7.73. Found: C, 69.40; H, 5.13; N, 7.74]. isolated The reaction mixture was cooled down purified by column chromatography, first using petroleum ether/dichloromethane (1:5) as an eluent

Conditions: temp:177.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: With reference to Scheme 3 below, a mixture of N-phthaloyl-DL-glutamic anhydride and phenethylamine was heated in a 177° C. oil bath. The reaction mixture was purified by chromatography on a silica gel column to afford N-phenethylthalidomide (8) and N-phenethylphthalimide (9). The reaction mixture was purified by chromatography on a silica gel column

Conditions: temp:177.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: With reference to Scheme 3 below, a mixture of N-phthaloyl-DL-glutamic anhydride and phenethylamine was heated in a 177° C. oil bath. The reaction mixture was purified by chromatography on a silica gel column to afford N-phenethylthalidomide (8) and N-phenethylphthalimide (9). The reaction mixture was purified by chromatography on a silica gel column

Conditions: temp:177.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1,3-Dioxo-2-(1-phenethyl-2,6-dioxopiperidin-3-yl)isoindoline (8) was specifically prepared and isolated as follows. A mixture of N-phthaloyl-DL-glutamic anhydride (300 mg, 1.13 mmol) and phenethylamine (139 mg, 1.13 mmol) was stirred in a 177° C. oil bath for two hours. The reaction mixture was cooled down and purified by column chromatography, first using petroleum ether/dichloromethane (1:5) as an eluent to afford N-phenethyl phthalimide as a pale yellow solid [1H NMR (CDCl3) δ 7.78-7.77 (m, 2 H), 7.65-7.62 (m 2H), 7.22-7.16 (m, 5 H), 3.83 (t, 2 H), 2.92 (t, 2H)], and then using dichloromethane as an eluent to afford N-phenethyl thalidomide as a syrup that was then recrystallized from ether to provide white crystals [(139 mg, 34%): mp 122-123° C.; 1H NMR (CDCl3) δ 7.84-7.81 (dd, J=3.1 Hz, J=5.4 Hz, 2H), 7.72-7.69 (dd, J=3.1 Hz, J=5.4 Hz, 2 H), 7.20-7.14 (m, 5 H), 4.89 (dd, J=5.4 Hz, J=12.5 Hz, 1 H), 4.01-3.92 (m, 2 H), 2.90-2.63 (m, 5 H), 2.06-2.02 (m, 1 H); Anal. Calcd for C21H18N2O4: C, 69.60; H, 5.01; N, 7.73. Found: C, 69.40; H, 5.13; N, 7.74]. isolated The reaction mixture was cooled down purified by column chromatography, first using petroleum ether/dichloromethane (1:5) as an eluent

Conditions: temp:177.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: With reference to Scheme 3 below, a mixture of N-phthaloyl-DL-glutamic anhydride and phenethylamine was heated in a 177° C. oil bath. The reaction mixture was purified by chromatography on a silica gel column to afford N-phenethylthalidomide (8) and N-phenethylphthalimide (9). The reaction mixture was purified by chromatography on a silica gel column

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

Procedure: After 2-phenylethyl alcohol (300 mg, 2.46 mmol), triphenylphosphine (775 mg, 2.95 mmol), phthalimide (434 mg, 2.95 mmol), and THF (12 ml) were added to a 50 ml flask, azodicarboxylic acid bis(2-methoxyethyl) ester (697 mg, 2.95 mmol) dissolved in THF (6 ml) was added dropwise thereto at 20° C., and the reaction was allowed to proceed for 2.5 hours. Water (0.5 mL) was added, and concentration was carried out. Then, water (10 ml) was added to the solution, and extraction was carried out using ethyl acetate (10 ml, ×2). Then, the organic layer was washed with water (10 mL) and saturated salt water (10 ml), and dehumidified with anhydrous magnesium sulfate. Subsequently, a crude product obtained by concentration was purified by column chromatography (silica gel, 30% ethyl acetate-hexane solution) to give 2-phenethyl isoindole-1,3-dione as a white solid substance (579 mg, yield: 94%/2-phenylethyl alcohol). was added dropwise at 20° C. concentration Then, water (10 ml) was added to the solution, and extraction Then, the organic layer was washed with water (10 mL) and saturated salt water (10 ml) Subsequently, a crude product obtained by concentration was purified by column chromatography (silica gel, 30% ethyl acetate-hexane solution)

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

Procedure: After 2-phenylethyl alcohol (300 mg, 2.46 mmol), triphenylphosphine (775 mg, 2.95 mmol), phthalimide (434 mg, 2.95 mmol), and THF (12 ml) were added to a 50 ml flask, azodicarboxylic acid bis(2-methoxyethyl) ester (697 mg, 2.95 mmol) dissolved in THF (6 ml) was added dropwise thereto at 20° C., and the reaction was allowed to proceed for 2.5 hours. Water (0.5 mL) was added, and concentration was carried out. Then, water (10 ml) was added to the solution, and extraction was carried out using ethyl acetate (10 ml, ×2). Then, the organic layer was washed with water (10 mL) and saturated salt water (10 ml), and dehumidified with anhydrous magnesium sulfate. Subsequently, a crude product obtained by concentration was purified by column chromatography (silica gel, 30% ethyl acetate-hexane solution) to give 2-phenethyl isoindole-1,3-dione as a white solid substance (579 mg, yield: 94%/2-phenylethyl alcohol). was added dropwise at 20° C. concentration Then, water (10 ml) was added to the solution, and extraction Then, the organic layer was washed with water (10 mL) and saturated salt water (10 ml) Subsequently, a crude product obtained by concentration was purified by column chromatography (silica gel, 30% ethyl acetate-hexane solution)

Conditions: temp:177.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1,3-Dioxo-2-(1-phenethyl-2,6-dioxopiperidin-3-yl)isoindoline (8) was specifically prepared and isolated as follows. A mixture of N-phthaloyl-DL-glutamic anhydride (300 mg, 1.13 mmol) and phenethylamine (139 mg, 1.13 mmol) was stirred in a 177° C. oil bath for two hours. The reaction mixture was cooled down and purified by column chromatography, first using petroleum ether/dichloromethane (1:5) as an eluent to afford N-phenethyl phthalimide as a pale yellow solid [1H NMR (CDCl3) δ 7.78-7.77 (m, 2H), 7.65-7.62 (m 2H), 7.22-7.16 (m, 5H), 3.83 (t, 2H), 2.92 (t, 2H)], and then using dichloromethane as an eluent to afford N-phenethyl thalidomide as a syrup that was then recrystallized from ether to provide white crystals [(139 mg, 34%): mp 122-123° C.; 1H NMR (CDCl3) δ 7.84-7.81 (dd, J=3.1 Hz, J=5.4 Hz, 2H), 7.72-7.69 (dd, J=3.1 Hz, J=5.4 Hz, 2H), 7.20-7.14 (m, 5H), 4.89 (dd, J=5.4 Hz, J=12.5 Hz, 1H), 4.01-3.92 (m, 2H), 2.90-2.63 (m, 5H), 2.06-2.02 (m, 1H); Anal. Calcd for C21H18N2O4: C, 69.60; H, 5.01; N, 7.73. Found: C, 69.40; H, 5.13; N, 7.74]. isolated The reaction mixture was cooled down purified by column chromatography, first using petroleum ether/dichloromethane (1:5) as an eluent

Conditions: temp:177.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1,3-Dioxo-2-(1-phenethyl-2,6-dioxopiperidin-3-yl)isoindoline (8) was specifically prepared and isolated as follows. A mixture of N-phthaloyl-DL-glutamic anhydride (300 mg, 1.13 mmol) and phenethylamine (139 mg, 1.13 mmol) was stirred in a 177° C. oil bath for two hours. The reaction mixture was cooled down and purified by column chromatography, first using petroleum ether/dichloromethane (1:5) as an eluent to afford N-phenethyl phthalimide as a pale yellow solid [1H NMR (CDCl3) δ 7.78-7.77 (m, 2H), 7.65-7.62 (m 2H), 7.22-7.16 (m, 5H), 3.83 (t, 2H), 2.92 (t, 2H)], and then using dichloromethane as an eluent to afford N-phenethyl thalidomide as a syrup that was then recrystallized from ether to provide white crystals [(139 mg, 34%): mp 122-123° C.; 1H NMR (CDCl3) δ 7.84-7.81 (dd, J=3.1 Hz, J=5.4 Hz, 2H), 7.72-7.69 (dd, J=3.1 Hz, J=5.4 Hz, 2H), 7.20-7.14 (m, 5H), 4.89 (dd, J=5.4 Hz, J=12.5 Hz, 1H), 4.01-3.92 (m, 2H), 2.90-2.63 (m, 5H), 2.06-2.02 (m, 1H); Anal. Calcd for C21H18N2O4: C, 69.60; H, 5.01; N, 7.73. Found: C, 69.40; H, 5.13; N, 7.74]. isolated The reaction mixture was cooled down purified by column chromatography, first using petroleum ether/dichloromethane (1:5) as an eluent

Conditions: temp:177.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: With reference to Scheme 3 below, a mixture of N-phthaloyl-DL-glutamic anhydride and phenethylamine was heated in a 177° C. oil bath. The reaction mixture was purified by chromatography on a silica gel column to afford N-phenethylthalidomide (8) and N-phenethylphthalimide (9). The reaction mixture was purified by chromatography on a silica gel column

Conditions: temp:177.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1,3-Dioxo-2-(1-phenethyl-2,6-dioxopiperidin-3-yl)isoindoline (8) was specifically prepared and isolated as follows. A mixture of N-phthaloyl-DL-glutamic anhydride (300 mg, 1.13 mmol) and phenethylamine (139 mg, 1.13 mmol) was stirred in a 177° C. oil bath for two hours. The reaction mixture was cooled down and purified by column chromatography, first using petroleum ether/dichloromethane (1:5) as an eluent to afford N-phenethyl phthalimide as a pale yellow solid [1H NMR (CDCl3) δ 7.78-7.77 (m, 2H), 7.65-7.62 (m 2H), 7.22-7.16 (m, 5H), 3.83 (t, 2H), 2.92 (t, 2H)], and then using dichloromethane as an eluent to afford N-phenethyl thalidomide as a syrup that was then recrystallized from ether to provide white crystals [(139 mg, 34%): mp 122-123° C.; 1H NMR (CDCl3) δ 7.84-7.81 (dd, J=3.1 Hz, J=5.4 Hz, 2H), 7.72-7.69 (dd, J=3.1 Hz, J=5.4 Hz, 2H), 7.20-7.14 (m, 5H), 4.89 (dd, J=5.4 Hz, J=12.5 Hz, 1H), 4.01-3.92 (m, 2H), 2.90-2.63 (m, 5H), 2.06-2.02 (m, 1H); Anal. Calcd for C21H18N2O4: C, 69.60; H, 5.01; N, 7.73. Found: C, 69.40; H, 5.13; N, 7.74]. isolated The reaction mixture was cooled down purified by column chromatography, first using petroleum ether/dichloromethane (1:5) as an eluent