Sodium Iodide → (Z)-5-fluoro-4-[1-iodo-3-oxo-3-(1H-pyrrol-2-yl)-propenyl]-1,3-dihydro-indol-2-one

HRID 1633763Notes

Reaction equation

HRID 1633763 reaction equation
C(OC([N:8]1[C:16]2[C:11](=[C:12]([C:18]#[C:19][C:20]([C:22]3[N:23](C(OC(C)(C)C)=O)[CH:24]=[CH:25][CH:26]=3)=[O:21])[C:13]([F:17])=[CH:14][CH:15]=2)[CH:10]=[C:9]1[O:34]C(OC(C)(C)C)=O)=O)(C)(C)C.[I-:42].[Na+].C(O)(C(F)(F)F)=O.C(=O)(O)[O-].[Na+]>C(OCC)(=O)C>[F:17][C:13]1[C:12](/[C:18](/[I:42])=[CH:19]/[C:20](=[O:21])[C:22]2[NH:23][CH:24]=[CH:25][CH:26]=2)=[C:11]2[C:16](=[CH:15][CH:14]=1)[NH:8][C:9](=[O:34])[CH2:10]2

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 102315682-tert-Butoxycarbonyloxy-4-[3-(1-tert-butoxycarbonyl-1H-pyrrol-2-yl)-3-oxo-prop-1-ynyl]-5-fluoro-indole-1-carboxylic acid tert-butyl ester

Product 1

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

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of 2-tert-butoxycarbonyloxy-4-[3-(1-tert-butoxycarbonyl-1H-pyrrol-2-yl)-3-oxo-prop-1-ynyl]-5-fluoro-indole-1-carboxylic acid tert-butyl ester (from Example 4 above) (5.90 g, 10.4 mmol) and sodium iodide (Aldrich, 4.67 g, 31.4 mmol) was added TFA (Aldrich, 35 mL) slowly at room temperature. The reaction mixture was stirred at room temperature for 30 minutes, and then poured into a mixture of a saturated aqueous sodium bicarbonate solution (400 mL) and ethyl acetate (500 mL). After separation, the aqueous layer was extracted with ethyl acetate (3×100 mL). The combined organic extracts were successively washed with water (200 mL) and brine (200 mL), dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The crude product was triturated with ethyl acetate, filtered, and dried to give (Z)-5-fluoro-4-[1-iodo-3-oxo-3-(1H-pyrrol-2-yl)-propenyl]-1,3-dihydro-indol-2-one as a brown solid which was used in the next step without further purification. (Yield 3.86 g, 93.7%).

Workup

  1. customAfter separation
  2. extractionthe aqueous layer was extracted with ethyl acetate (3×100 mL)
  3. washThe combined organic extracts were successively washed with water (200 mL) and brine (200 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude product was triturated with ethyl acetate
  8. filtrationfiltered
  9. customdried

Sources & evidence

ORD record
ord-17ebdeb8b5464867afb5b6a986846da0
Source dataset
uspto-grants-2003_01
Patent number
US06504034B2

Reaction notes

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