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

HRID 533360Notes

Reaction equation

HRID 533360 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-dc2da9662d7d4c2984161ee8c08bd700
Source dataset
uspto-grants-2014_10
Patent number
US08853253B2

Reaction notes

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