Phthalic Anhydride → 2-((5-Bromo-3-chloropyridin-2-yl)methyl)isoindoline-1,3-dione

HRID 1503003Notes

Reaction equation

HRID 1503003 reaction equation
Cl.[Br:2][C:3]1[CH:4]=[C:5]([Cl:11])[C:6]([CH2:9][NH2:10])=[N:7][CH:8]=1.[C:12]1(=O)[O:17][C:15](=[O:16])[C:14]2=[CH:18][CH:19]=[CH:20][CH:21]=[C:13]12>C1(C)C=CC=CC=1>[Br:2][C:3]1[CH:4]=[C:5]([Cl:11])[C:6]([CH2:9][N:10]2[C:15](=[O:16])[C:14]3[C:13](=[CH:21][CH:20]=[CH:19][CH:18]=3)[C:12]2=[O:17])=[N:7][CH:8]=1

Participants

4

Reactant 2

HCID 6811Phthalic AnhydrideHCID 71138342(5-Bromo-3-chloropyridin-2-yl)methanamine hydrochloride

Product 1

HCID 711385752-((5-Bromo-3-chloropyridin-2-yl)methyl)isoindoline-1,3-dioneYield 65%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a stirred solution of (5-bromo-3-chloropyridin-2-yl)methanamine hydrochloride (0.3 g, 1.4 mmol) in toluene (40 mL) was added TEA (0.41 g, 4.08 mmol) and phthalic anhydride (0.24 g, 1.63 mmol), and the reaction mixture was heated at reflux for 2 h. The reaction mixture was concentrated under reduced pressure, and the residue was diluted with water and extracted with EtOAc. The combined EtOAc layer was washed with brine, dried over anhydrous Na2SO4, and concentrated under reduced pressure. The residue was purified by column chromatography (20-30% EtOAc in hexane) to afford the title compound as a white solid (0.25 g, 65%): 1H NMR (400 MHz, CDCl3) δ 8.78 (s, 1H), 8.45 (s, 1H), 7.88 (m, 2H), 7.74 (m, 2H), 4.56 (m, 2H); ESIMS m/z 349 ([M−H]−); IR (thin film) 3307, 1665, 1114, 813 cm−1.

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureat reflux for 2 h
  3. concentrationThe reaction mixture was concentrated under reduced pressure
  4. additionthe residue was diluted with water
  5. extractionextracted with EtOAc
  6. washThe combined EtOAc layer was washed with brine
  7. dry with materialdried over anhydrous Na2SO4
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by column chromatography (20-30% EtOAc in hexane)

Sources & evidence

ORD record
ord-ae142c3aabb74231be042278a0fecfbf
Source dataset
uspto-grants-2015_12
Patent number
US09211281B2

Reaction notes

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