Toluene → 2-((3-Chloro-5-vinylpyridin-2-yl)methyl)isoindoline-1,3-dione

HRID 1503004Notes

Reaction equation

HRID 1503004 reaction equation
Br[C:2]1[CH:3]=[C:4]([Cl:20])[C:5]([CH2:8][N:9]2[C:17](=[O:18])[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10]2=[O:19])=[N:6][CH:7]=1.C([O-])([O-])=O.[K+].[K+].[C:27]1(C)C=CC=C[CH:28]=1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:20][C:4]1[C:5]([CH2:8][N:9]2[C:17](=[O:18])[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10]2=[O:19])=[N:6][CH:7]=[C:2]([CH:27]=[CH2:28])[CH:3]=1

Participants

5

Reactant 3

HCID 1140TolueneHCID 11430Potassium CarbonateHCID 711385752-((5-Bromo-3-chloropyridin-2-yl)methyl)isoindoline-1,3-dione

Product 1

HCID 866751842-((3-Chloro-5-vinylpyridin-2-yl)methyl)isoindoline-1,3-dioneYield 65%

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Procedure

To a stirred solution of 2-((5-bromo-3-chloropyridin-2-yl)methyl)isoindoline-1,3-dione (CI.23 g, 0.65 mmol) in toluene (10 mL) were added Pd(PPh3)4 (3.7 mg, 0.003 mmol), K2CO3 (0.269 g, 1.95 mmol) and vinyl boronic anhydride pyridine complex (0.78 g, 3.28 mmol), and the reaction mixture was heated at reflux for 16 h. The reaction mixture was filtered, and the filtrate was washed with water and brine, dried over anhydrous Na2SO4, and concentrated under reduced pressure. Purification by flash column chromatography (20-30% EtOAc in hexane) afforded the title compound as an off-white solid (0.2 g, 65%): 1H NMR (400 MHz, CDCl3) δ 8.30 (s, 1H), 7.91 (m, 2H), 7.77 (m, 3H), 7.72 (m, 1H), 6.63 (m, 1H), 5.79 (d, J=16.0 Hz, 1H), 5.39 (d, J=16.0 Hz, 1H), 5.12 (s, 2H); ESIMS m/z 299.20 ([M+H]+).

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureat reflux for 16 h
  3. filtrationThe reaction mixture was filtered
  4. washthe filtrate was washed with water and brine
  5. dry with materialdried over anhydrous Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customPurification by flash column chromatography (20-30% EtOAc in hexane)

Sources & evidence

ORD record
ord-613646b71ca5440aa5ecd105cdb85944
Source dataset
uspto-grants-2015_12
Patent number
US09211281B2

Reaction notes

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