Phenethylamine → N-phenethyl phthalimide

HRID 1009082Notes

Reaction equation

HRID 1009082 reaction equation
[O:1]=[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:11])[N:3]1[CH:12]1[CH2:17][CH2:16][C:15](=O)N(CCC2C=CC=CC=2)C1=O.[CH2:28]1[CH:35](N2C(=O)C3C(=CC=CC=3)C2=O)C(=O)O[C:30](=O)[CH2:29]1.C(N)CC1C=CC=CC=1>>[CH2:12]([N:3]1[C:4](=[O:11])[C:5]2=[CH:6][CH:7]=[CH:8][CH:9]=[C:10]2[C:2]1=[O:1])[CH2:17][C:16]1[CH:15]=[CH:30][CH:29]=[CH:28][CH:35]=1

Participants

4

Reactant 3

HCID 1001PhenethylamineHCID 921931H-Isoindole-1,3(2H)-dione, 2-(tetrahydro-2,6-dioxo-2H-pyran-3-yl)-HCID 11417136HCID 11417136, compound

Product 1

HCID 348641N-phenethyl phthalimide

Conditions

Temperature
177 °C

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].

Workup

  1. customisolated
  2. temperatureThe reaction mixture was cooled down
  3. custompurified by column chromatography, first using petroleum ether/dichloromethane (1:5) as an eluent

Sources & evidence

ORD record
ord-e9be55c364db4b3cb7add339186d3747
Source dataset
uspto-grants-2011_07
Patent number
US07973057B2

Reaction notes

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