Sodium hydride → Tert-butyl 2-(6-fluoro-2,3-dioxoindolin-1-yl)acetate

HRID 571261Notes

Reaction equation

HRID 571261 reaction equation
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6](=[O:12])[C:7](=[O:11])[NH:8]2)=[CH:4][CH:3]=1.[H-].[Na+].Br[CH2:16][C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18]>CN(C=O)C>[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6](=[O:12])[C:7](=[O:11])[N:8]2[CH2:16][C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 79177tert-Butyl bromoacetateHCID 3739056-Fluoroisatin

Product 1

HCID 86681676Tert-butyl 2-(6-fluoro-2,3-dioxoindolin-1-yl)acetateYield 65%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 6-fluoroindoline-2,3-dione (2 g, 12.11 mmol) in dry DMF (100 ml) was cooled to 0° C., and NaH (60% w/w dispersion in mineral oil; 0.484 g, 12.11 mmol) was added portion wise over 10 minutes. The mixture was stirred at the same temperature for 10 minutes, then tert-butyl 2-bromoacetate (1.788 ml, 12.11 mmol) was added drop wise. The mixture was left warm to room temperature and stirred for 2 hours. DMF was evaporated under vacuum, and the crude was portioned between ethyl acetate (50 ml) and aqueous 1N HCl (40 ml). The aqueous phase was extracted with ethyl acetate (2×50 ml), and the combined organic layers were dried over sodium sulfate, filtered and concentrate under vacuum. The crude was purified by flash chromatography on silica gel cartridge (petroleum ether:ethyl acetate=80:20) affording tert-butyl 2-(6-fluoro-2,3-dioxoindolin-1-yl)acetate

Workup

  1. waitThe mixture was left
  2. stirringstirred for 2 hours
  3. customDMF was evaporated under vacuum
  4. extractionThe aqueous phase was extracted with ethyl acetate (2×50 ml)
  5. dry with materialthe combined organic layers were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrate under vacuum
  8. customThe crude was purified by flash chromatography on silica gel cartridge (petroleum ether:ethyl acetate=80:20)

Sources & evidence

ORD record
ord-606c6d699f024aacad8bba7883088d72
Source dataset
uspto-grants-2015_05
Patent number
US09024027B2

Reaction notes

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