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

HRID 618694Notes

Reaction equation

HRID 618694 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[CH:12]1[CH2:17][CH2:16][C:15](=[O:18])[N:14](C(OC(C)(C)C)=O)[C:13]1=[O:26].C([N-]C(C)C)(C)C.[Li+].Cl([F:39])(=O)(=O)=O>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:39])[CH2:17][CH2:16][C:15](=[O:18])[NH:14][C:13]1=[O:26]

Participants

4

Reactant 2

HCID 2724682Lithium diisopropylamideHCID 15408802Tert-butyl 3-(1,3-dioxoisoindolin-2-yl)-2,6-dioxopiperidine-1-carboxylate

Product 1

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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 1,3-dioxo-2-(1-tert.-butoxycarbonyl-2,6-dioxopiperidin-3-yl)isoindoline (1.0 g. 2.8 mmol) in tetrahydrofuran (10 mL) is added lithium diisopropylamide (1.5 mL, 3.0 mmol, 2 M) at. After 30 minutes, perchloryl fluoride (5 mmol) is bubbled into the mixture. The mixture is allowed to reach room temperature and the solvent then removed in vacuo. The residue is stirred with ethyl acetate (10 mL) and 1N hydrochloric acid (10 mL) for one hour. The organic layer is separated and the solvent removed in vacuo to yield 1,3-dioxo-2-(2,6-dioxo-3-fluoropiperidin-3-yl)isoindoline which can be further purified through chromatography.

Workup

  1. customto reach room temperature
  2. customthe solvent then removed in vacuo
  3. customThe organic layer is separated
  4. customthe solvent removed in vacuo

Sources & evidence

ORD record
ord-eb32bc8cf32e4b10ab1ea3d845a98ae6
Source dataset
uspto-grants-1999_09
Patent number
US05955476

Reaction notes

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