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

HRID 363441Notes

Reaction equation

HRID 363441 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, 2M) 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-ad788feeae5a41e9b9b926821f3e9d1c
Source dataset
uspto-grants-1999_02
Patent number
US05874448

Reaction notes

Loading…