2-Dimethylaminopyrimidine → 1,3-Dioxo-2-(2,6-dioxo-3-fluoropiperidin-3-yl)isoindoline

HRID 618704Notes

Reaction equation

HRID 618704 reaction equation
[O:1]=[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:11])[N:3]1[C:12]([C:19]([O:21]CC)=O)([F:18])[CH2:13][CH2:14][C:15](O)=[O:16].C(C1NC=CN=1)(C1[NH:27]C=CN=1)=O.CN(C1N=CC=CN=1)C>O1CCCC1>[O:1]=[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:11])[N:3]1[C:12]1([F:18])[CH2:13][CH2:14][C:15](=[O:16])[NH:27][C:19]1=[O:21]

Participants

5

Reactant 3

HCID 5217172-DimethylaminopyrimidineHCID 5250894Bis-(1H-imidazol-2-YL)-methanoneHCID 218479184-(1,3-Dioxoisoindolin-2-yl)-4-(ethoxycarbonyl)-4-fluorobutanoic acid

Product 1

HCID 98820501,3-Dioxo-2-(2,6-dioxo-3-fluoropiperidin-3-yl)isoindoline

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 4-(1,3-dioxoisoindolin-2-yl)-4-(ethoxycarbonyl)-4-fluorobutanoic acid (0.9 g, 2.8 mmol), carbonyl diimidazole (0.46 g, 2.8 mmol) and dimethylaminopyrimidine (0.68 g, 5.6 mmol) in tetrahydrofuran (30 mL) is heated at reflux for 18 hours. The solvent is removed in vacuo and the residue is stirred with methylene chloride (50 mL) for 10 minutes. The organic layer is washed with water and brine (40 mL each) and dried over sodium sulfate. The solvent is removed in vacuo to give 1,3-dioxo-2-(2,6-dioxo-3-fluoropiperidin-3-yl)isoindoline which is further purified by column chromatography.

Workup

  1. temperatureis heated
  2. temperatureat reflux for 18 hours
  3. customThe solvent is removed in vacuo
  4. washThe organic layer is washed with water and brine (40 mL each)
  5. dry with materialdried over sodium sulfate
  6. customThe solvent is removed in vacuo

Sources & evidence

ORD record
ord-19f0cbea206c402299780493cbd1ca8d
Source dataset
uspto-grants-1999_09
Patent number
US05955476

Reaction notes

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