Triethylamine → 2-[(Pyridin-4-yl)methoxy]-1H-isoindole-1,3(2H)-dione

HRID 2395815Notes

Reaction equation

HRID 2395815 reaction equation
[OH:1][N:2]1[C:6](=[O:7])[C:5]2=[CH:8][CH:9]=[CH:10][CH:11]=[C:4]2[C:3]1=[O:12].Cl.[N:14]1[CH:19]=[CH:18][C:17]([CH2:20]Cl)=[CH:16][CH:15]=1.C(N(CC)CC)C>C(#N)C>[N:14]1[CH:19]=[CH:18][C:17]([CH2:20][O:1][N:2]2[C:3](=[O:12])[C:4]3[C:5](=[CH:8][CH:9]=[CH:10][CH:11]=3)[C:6]2=[O:7])=[CH:16][CH:15]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 10665N-HydroxyphthalimideHCID 745704-(Chloromethyl)pyridinium chloride

Product 1

HCID 152797472-[(Pyridin-4-yl)methoxy]-1H-isoindole-1,3(2H)-dioneYield 57.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Under anhydrous conditions (positive nitrogen pressure, presence of 3Å molecular sieves), a mixture of N-hydroxyphthalimide (15.0g, 0.091mole), 4-picolylchloride hydrochloride (15.0g, 0.091mole), and triethylamine (27.7g, 0.273 mol) in 125 ml of anhydrous acetonitrile was refluxed for 2 hours. After stirring overnight at ambient temperature, TLC showed that the starting materials were practically consumed. Ethyl acetate (500 ml) was added, mixture stirred for 15 min and filtered. The solvent was evaporated and the residue dissolved in 1L of EtOAc. The filtrate was washed with water (2×500 ml), brine (1×500 ml), dried (MgSO4), and evaporated to a smaller volume (100ml). The mixture was cooled down to -18° C., precipitate filtered and recrystallized from EtOAc/hexane to afford 13.2g (56.8%) of title product.

Workup

  1. temperaturewas refluxed for 2 hours
  2. customwere practically consumed
  3. additionEthyl acetate (500 ml) was added
  4. stirringmixture stirred for 15 min
  5. filtrationfiltered
  6. customThe solvent was evaporated
  7. dissolutionthe residue dissolved in 1L of EtOAc
  8. washThe filtrate was washed with water (2×500 ml), brine (1×500 ml)
  9. dry with materialdried (MgSO4)
  10. customevaporated to a smaller volume (100ml)
  11. temperatureThe mixture was cooled down to -18° C.
  12. filtrationprecipitate filtered
  13. customrecrystallized from EtOAc/hexane

Sources & evidence

ORD record
ord-760b099940e541a8bc9ae43edda7ea2c
Source dataset
uspto-grants-1996_02
Patent number
US05489680

Reaction notes

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