Phthalic anhydride, 3-acetoxy- → 1,3-Dioxo-2-(2,6-dioxopiperidin-3-yl)-4-acetoxyisoindoline

HRID 1009084Notes

Reaction equation

HRID 1009084 reaction equation
[C:1]([O:4][C:5]1[CH:15]=[CH:14][CH:13]=[C:7]2[C:8]([O:10][C:11](=[O:12])[C:6]=12)=O)(=[O:3])[CH3:2].FC(F)(F)C(O)=O.[NH2:23][CH:24]1[CH2:30][CH2:29][C:28](=[O:31])[NH:27][C:25]1=[O:26].CC([O-])=O.[Na+]>C(O)(=O)C>[O:10]=[C:8]1[C:7]2[C:6](=[C:5]([O:4][C:1](=[O:3])[CH3:2])[CH:15]=[CH:14][CH:13]=2)[C:11](=[O:12])[N:23]1[CH:24]1[CH2:30][CH2:29][C:28](=[O:31])[NH:27][C:25]1=[O:26]

Participants

5

Reactant 3

HCID 294175Phthalic anhydride, 3-acetoxy-HCID 517045Sodium AcetateHCID 53447112Trifluoroacetic acid--3-aminopiperidine-2,6-dione (1/1)

Product 1

HCID 250152191,3-Dioxo-2-(2,6-dioxopiperidin-3-yl)-4-acetoxyisoindolineYield 66%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

1,3-Dioxo-2-(2,6-dioxopiperidin-3-yl)-4-acetoxyisoindoline was prepared and isolated as follows. A mixture of 3-acetoxyphthalic anhydride (40 mg), aminoglutarimide trifluoroacetate (47 mg), and NaOAc (32 mg) in acetic acid (2 mL) was refluxed for 5 h. The solvent was evaporated, water (10 mL) was added, and the resulting solution was stirred for several minutes. The solid was filtered out and recrystallized from ethyl acetate to give 1,3-dioxo-2-(2,6-dioxopiperidin -3-yl)-4-acetoxyisoindoline as pale yellow crystals (35 mg, 66%): 1H NMR (DMSO) δ 11.16 (s, 1H), 11.07 (s, 1H), 7.64 (t, J=7.2 Hz, 1H), 7.22-7.31 (m, 2H), 5.05 (dd, J=5.4 Hz, J=12.5 Hz, 1H), 2.87-2.92 (m, 2H), 2.48 (s, 3H), 2.08-2.00 (m, 2H).

Workup

  1. custom1,3-Dioxo-2-(2,6-dioxopiperidin-3-yl)-4-acetoxyisoindoline was prepared
  2. customisolated
  3. temperaturewas refluxed for 5 h
  4. customThe solvent was evaporated
  5. additionwater (10 mL) was added
  6. filtrationThe solid was filtered out
  7. customrecrystallized from ethyl acetate

Sources & evidence

ORD record
ord-84cf24d450884943a430e5844372c95d
Source dataset
uspto-grants-2011_07
Patent number
US07973057B2

Reaction notes

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