tert-Butyl acrylate → Tert-butyl 4-(1,3-dioxoisoindolin-2-yl)-4-fluoro-4-ethoxycarbonylbutanoate

HRID 618702Notes

Reaction equation

HRID 618702 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]([F:18])[C:13]([O:15][CH2:16][CH3:17])=[O:14].C([N-]C(C)C)(C)C.[Li+].[C:27]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])(=[O:30])[CH:28]=[CH2:29]>O1CCCC1>[O:11]=[C:4]1[C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[C:2](=[O:1])[N:3]1[C:12]([F:18])([C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH2:29][CH2:28][C:27]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30]

Participants

5

Reactant 3

HCID 15458tert-Butyl acrylateHCID 2724682Lithium diisopropylamideHCID 13594881Ethyl 2-(1,3-dioxoisoindolin-2-yl)-2-fluoroacetate

Product 1

HCID 54501069Tert-butyl 4-(1,3-dioxoisoindolin-2-yl)-4-fluoro-4-ethoxycarbonylbutanoate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of ethyl 2-(1,3-dioxoisoindolin-2-yl)-2-fluoroacetate (0.80 g, 3.2 mmol) in tetrahydrofuran (30 mL) is added lithium diisopropylamide (1.7 mL, 3.4 mmol, 2 M) at -78° C. After 30 minutes, t-butyl acrylate (0.42 g, 3.2 mmol) is added to the mixture which is allowed to reach room temperature. The solvent is removed in vacuo and the residue stirred with methylene chloride (50 mL) and water (30 mL) for 10 min. The organic layer is washed with brine (30 mL), and dried over sodium sulfate. The solvent is removed in vacuo to give tert-butyl 4-(1,3-dioxoisoindolin-2-yl)-4-fluoro-4-ethoxycarbonylbutanoate which is further purified by column chromatography.

Workup

  1. customto reach room temperature
  2. customThe solvent is removed in vacuo
  3. washThe organic layer is washed with brine (30 mL)
  4. dry with materialdried over sodium sulfate
  5. customThe solvent is removed in vacuo

Sources & evidence

ORD record
ord-9ef903f8855141efa4a361e0e3776543
Source dataset
uspto-grants-1999_09
Patent number
US05955476

Reaction notes

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