N,N,N',N'-Tetramethylethylenediamine → 1,3-Dioxo-2-(2,6-dioxo-3-fluoropiperidin-3-yl)isoindoline

HRID 363435Notes

Reaction equation

HRID 363435 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].CN(C)CCN(C)C.C([Li])CCC.C1C=CC(S(N(S(C2C=CC=CC=2)(=O)=O)[F:50])(=O)=O)=CC=1>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:50])[CH2:17][CH2:16][C:15](=[O:18])[NH:14][C:13]1=[O:26]

Participants

6

Reactant 4

HCID 8037N,N,N',N'-TetramethylethylenediamineHCID 588007N-FluorobenzenesulfonimideHCID 15408802Tert-butyl 3-(1,3-dioxoisoindolin-2-yl)-2,6-dioxopiperidine-1-carboxylateHCID 178418339Butyllithium

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) and tetramethylethylene diamine (0.5 g, 4.3 mmol) in tetrahydrofuran (10 mL) is added n-butyl lithium (1.2 mL, 3.0 mmol, 2.5 M) at -78° C. After 30 minutes, N-fluorobenzenesulfonimide (0-8 g, 3.2 mmol) is added to 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 IN 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 column 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-3e10aa7fd35a45198852a3432d6b7278
Source dataset
uspto-grants-1999_02
Patent number
US05874448

Reaction notes

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