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

HRID 1693089Notes

Reaction equation

HRID 1693089 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) δ 11.18(s, 1H), 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 (DMSO)-d6) δ 172.66, 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-7d8f8278328749b5b7ae342a4c1a1e20
Source dataset
uspto-grants-2012_04
Patent number
US08158653B2

Reaction notes

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