4-Bromophthalic anhydride → 5-Bromo-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione

HRID 331612Notes

Reaction equation

HRID 331612 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[O:10])[O:8][C:6](=O)[C:5]2=[CH:11][CH:12]=1.Cl.[NH2:14][CH:15]1[CH2:21][CH2:20][C:19](=[O:22])[NH:18][C:16]1=[O:17].C([O-])(=O)C.[Na+]>C(O)(=O)C>[Br:1][C:2]1[CH:3]=[C:4]2[C:5](=[CH:11][CH:12]=1)[C:6](=[O:8])[N:14]([CH:15]1[CH2:21][CH2:20][C:19](=[O:22])[NH:18][C:16]1=[O:17])[C:9]2=[O:10]

Participants

5

Reactant 3

HCID 665904-Bromophthalic anhydrideHCID 1345483-Aminopiperidine-2,6-dione hydrochlorideHCID 517045Sodium Acetate

Product 1

HCID 444356805-Bromo-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dioneYield 93%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

A mixture of 4-bromophthalic anhydride (10.0 g, 44.1 mmol), rac-α-aminoglutarimide hydrochloride (7.25 g, 44.0 mmol) and sodium acetate (3.61 g, 44.0 mmol) in acetic acid (150 mL) was heated to reflux overnight. The reaction mixture was cooled to room temperature, and the solvent was evaporated under vacuum. The residue was stirred in water (170 mL) for 3 hours, and the resulting solid was filtered, washed with additional water (80 mL), and dried under vacuum, to afford 13.8 g of 5-bromo-2-(2,6-dioxo-piperidin-3-yl)-isoindole-1,3-dione, in 93% yield; 1H NMR (DMSO-d6) δ 2.03-2.10 (m, 1H), 2.43-2.63 (m, 2H), 2.82-2.97 (m, 1H), 5.17 (dd, J=12.8 Hz, J=5.3 Hz, 1H), 7.85-7.88 (d, J=7.9 Hz, 1H), 8.10 (dd, J=7.9 Hz, J=1.7 Hz, 1H), 8.16 (d, J=1.7 Hz, 1H), 11.15 (s, 1H); 13C NMR (DMSO-d6) δ 21.9, 30.9, 49.2, 125.3, 126.4, 128.5, 130.1, 133.2, 137.6, 165.9, 166.4, 169.7, 172.7; Anal. Calcd for C13H9N2O4Br: C, 46.32; H, 2.69; N, 8.31. Found: C, 46.23; H, 2.47; N, 8.41.

Workup

  1. temperaturewas heated
  2. temperatureto reflux overnight
  3. customthe solvent was evaporated under vacuum
  4. filtrationthe resulting solid was filtered
  5. washwashed with additional water (80 mL)
  6. customdried under vacuum

Sources & evidence

ORD record
ord-7206bde7fee347afacd58b1abee10f31
Source dataset
uspto-grants-2014_11
Patent number
US08877780B2

Reaction notes

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