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

HRID 363443Notes

Reaction equation

HRID 363443 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-87dd17856fa543278461261f0b8735db
Source dataset
uspto-grants-1999_02
Patent number
US05874448

Reaction notes

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