Ethylene Glycol → 6-Fluoro-5-(2-hydroxy-ethoxy)-3-(1H-pyrrol-2-yl)-1H-benzo[cd]indol-2-one

HRID 1860994Notes

Reaction equation

HRID 1860994 reaction equation
[F:1][C:2]1[C:3](/[C:12](/I)=[CH:13]/[C:14](=O)[C:15]2[NH:16][CH:17]=[CH:18][CH:19]=2)=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])[CH2:5]2.[H-].[Na+].[CH2:24]([OH:27])[CH2:25][OH:26]>>[F:1][C:2]1[C:3]2[C:4]3[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])[C:5]=3[C:14]([C:15]1[NH:16][CH:17]=[CH:18][CH:19]=1)=[CH:13][C:12]=2[O:26][CH2:25][CH2:24][OH:27]

Participants

4

Reactant 3

HCID 174Ethylene GlycolHCID 24758Sodium hydrideHCID 10135347(Z)-5-fluoro-4-[1-iodo-3-oxo-3-(1H-pyrrol-2-yl)-propenyl]-1,3-dihydro-indol-2-one

Product 1

HCID 102676636-Fluoro-5-(2-hydroxy-ethoxy)-3-(1H-pyrrol-2-yl)-1H-benzo[cd]indol-2-one

Procedure

To a suspension of (Z)-5-fluoro-4-[1-iodo-3-oxo-3-(1H-pyrrol-2-yl)-propenyl]-1,3-dihydro-indol-2-one (from Example 8 above) (396 mg, 1.0 mmol) in ethylene glycol (Fisher Scientific, 60 mL) was added NaH (Aldrich, 95%, 2.0 g, 79.2 mmol) in portions at room temperature. After stirring at room temperature for 30 minutes, the reaction mixture was heated under reflux for 2 hours. The reaction was quenched by pouring the reaction mixture into an ice-cold saturated aqueous ammonium chloride solution (100 mL) and extracted with ethyl acetate (3×200 mL). The combined organic extracts were successively washed with water (100 mL) and brine (100 mL), dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The crude product was purified by flash chromatography (silica gel, 50% ethyl acetate in hexanes) to give 6-fluoro-5-(2-hydroxy-ethoxy)-3-(1H-pyrrol-2-yl)-1H-benzo[cd]indol-2-one as a yellow solid. (Yield 127.0 mg, 40.7%).

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureunder reflux for 2 hours
  3. customThe reaction was quenched
  4. additionby pouring the reaction mixture into an ice-cold saturated aqueous ammonium chloride solution (100 mL)
  5. extractionextracted with ethyl acetate (3×200 mL)
  6. washThe combined organic extracts were successively washed with water (100 mL) and brine (100 mL)
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe crude product was purified by flash chromatography (silica gel, 50% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-42e8550054c0411a8014e1618f9b43f4
Source dataset
uspto-grants-2003_03
Patent number
US06531598B1

Reaction notes

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