3-Aminopiperidine-2,6-dione hydrochloride → 2-(2,6-Dioxopiperidin-3-yl)-5-nitro-1H-isoindole-1,3(2H)-dione

HRID 1249766Notes

Reaction equation

HRID 1249766 reaction equation
[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[O:12])[O:10][C:8](=O)[C:7]2=[CH:13][CH:14]=1)([O-:3])=[O:2].Cl.[NH2:16][CH:17]1[CH2:23][CH2:22][C:21](=[O:24])[NH:20][C:18]1=[O:19].C([O-])(=O)C.[Na+]>C(O)(=O)C>[O:10]=[C:8]1[C:7]2[C:6](=[CH:5][C:4]([N+:1]([O-:3])=[O:2])=[CH:14][CH:13]=2)[C:11](=[O:12])[N:16]1[CH:17]1[CH2:23][CH2:22][C:21](=[O:24])[NH:20][C:18]1=[O:19]

Participants

5

Reactant 3

HCID 1345483-Aminopiperidine-2,6-dione hydrochlorideHCID 2309764-Nitrophthalic acid anhydrideHCID 517045Sodium Acetate

Product 1

HCID 155520312-(2,6-Dioxopiperidin-3-yl)-5-nitro-1H-isoindole-1,3(2H)-dioneYield 54.3%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

A mixture of 4-nitrophthalic anhydride (1.7 g. 8.5 mmol), α-aminoglutarimide hydrochloride (1.4 g, 8.5 mmol) and sodium acetate (0.7 g, 8.6 mmol) in glacial acetic acid (30 mL) was heated under reflux for 17 hours. The mixture was concentrated in vacuo and the residue was stirred with methylene chloride (40 mL) and water (30 mL). The aqueous layer was separated, extracted with methylene chloride (2×40 mL). The combined methylene chloride solutions were dried over magnesium sulfate and concentrated in vacuo to give 1.4 g (54%) of 1,3-dioxo-2-(2,6-dioxopiperidin-3-yl)-5-nitroisoindoline as a light brown solid. An analytical sample was obtained by recrystallization from methanol: mp 228.5-229.5° C.; 1H NMR (DMSO-d6) δ11.18(s, 1 H), 8.69-8.65(d,d J=1.9 and 8.0 Hz, 1H), 8.56(d, J=1.9 Hz, 1H), 8.21(d, H=8.2 Hz, 1H), 5.28(d,d J=5.3 and 12.8 Hz, 1H), 2.93-2.07(m, 4H); 13C NMR (DNMSO-d6) δ172.66, 169.47, 165.50, 165.23, 151.69, 135.70, 132.50. 130.05, 124.97, 118.34, 49.46, 30.85, 21.79; Anal. Calcd for C13H9N3O6: C, 51.49; H, 2.99; N, 13.86. Found: C, 51.59; H, 3.07; N, 13.73.

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 17 hours
  3. concentrationThe mixture was concentrated in vacuo
  4. customThe aqueous layer was separated
  5. extractionextracted with methylene chloride (2×40 mL)
  6. dry with materialThe combined methylene chloride solutions were dried over magnesium sulfate
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-750a17510f2d41ca95411b1e5865ad31
Source dataset
uspto-grants-2002_01
Patent number
US06335349B1

Reaction notes

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