Phthalic Anhydride → 2-(4-Pyridinylmethyl)-1H-isoindole-1,3(2H)-dione

HRID 1585239Notes

Reaction equation

HRID 1585239 reaction equation
[C:1]1(=[O:11])[O:6][C:4](=O)[C:3]2=[CH:7][CH:8]=[CH:9][CH:10]=[C:2]12.C(N(CC)CC)C.[NH2:19][CH2:20][C:21]1[CH:26]=[CH:25][N:24]=[CH:23][CH:22]=1>C1(C)C(C)=CC=CC=1>[N:24]1[CH:25]=[CH:26][C:21]([CH2:20][N:19]2[C:1](=[O:11])[C:2]3[C:3](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:4]2=[O:6])=[CH:22][CH:23]=1

Participants

5

Reactant 3

HCID 6811Phthalic AnhydrideHCID 8471TriethylamineHCID 773174-Pyridinemethanamine

Product 1

HCID 27316422-(4-Pyridinylmethyl)-1H-isoindole-1,3(2H)-dioneYield 78.9%

Reagents, catalysts & solvents 1

HCID 7237O-XyleneSolvent

Procedure

To a mixture of 148.0 g (1.0 mol) of phthalic anhydride and 15 mL of triethylamine in 1.5 L of xylene was slowly added 108.0 g (1.0 mol) of 4-(Aminomethyl)pyridine with mechanical stirring. The resulting solid was collected by filtration. The N-Pyridin-4-ylmethyl-phthalamic acid was then cyclized, by heating 235 g (0.88 mol) to the melt stage for 15 min. The mixture was allowed to cool slightly and 2.5 L of ethanol was added to the warm reaction mixture, and the solution filtered. Upon cooling, the mixture crystallized to give 188.0 g of 2-Pyridin-4-ylmethyl-isoindole-1,3-dione (m.p. 166-167.5° C.). A mixture of 23.8 g (0.1 mol) of 2-Pyridin-4-ylmethyl-isoindole-1,3-dione and 1.3 g of platinum oxide in 400 mL of methanolic HCl was reduced at 50 psi until no starting material could be detected by TLC. The mixture was filtered through celite and concentrated to give 22.0 g of 2-Piperidin-4-ylmethyl-isoindole-1,3-dione hydrochloride as a white solid. A small sample was recrystallized from ethanol to give an analytically pure sample of 16A (m.p. 241-242.5° C.).

Workup

  1. filtrationThe resulting solid was collected by filtration
  2. temperatureby heating 235 g (0.88 mol) to the melt stage for 15 min
  3. temperatureto cool slightly
  4. addition2.5 L of ethanol was added to the warm reaction mixture
  5. filtrationthe solution filtered
  6. temperatureUpon cooling
  7. customthe mixture crystallized

Sources & evidence

ORD record
ord-41902d5a55d6416daee3dddd82cd041c
Source dataset
uspto-grants-1999_08
Patent number
US05936089

Reaction notes

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