Sodium hydride → N-(3-fluoro-4-(2-(2-hydroxyethyl)acryloyl)phenyl)pyridine-2-carboxamide

HRID 13392

Reaction equation

HRID 13392 reaction equation
[H-].[Na+].Br[C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=2)=[O:12])=[CH:6][C:5]=1[F:19].C([Li])CCC.[CH2:25]=[C:26]1[CH2:30][CH2:29][O:28][C:27]1=[O:31].C(=O)(O)[O-].[Na+]>O1CCCC1>[F:19][C:5]1[CH:6]=[C:7]([NH:10][C:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=2)=[O:12])[CH:8]=[CH:9][C:4]=1[C:27](=[O:31])[C:26]([CH2:30][CH2:29][OH:28])=[CH2:25]

Participants

7

Reactant 5

HCID 24758Sodium hydrideHCID 68352alpha-Methylene butyrolactoneHCID 516892Sodium BicarbonateHCID 23145244N-(4-bromo-3-fluorophenyl)pyridine-2-carboxamideHCID 178418339Butyllithium

Product 1

HCID 23145344N-(3-fluoro-4-(2-(2-hydroxyethyl)acryloyl)phenyl)pyridine-2-carboxamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

136 mg of 60% sodium hydride was added to a tetrahydrofuran (20 ml) solution of 1.0 g of N-(4-bromo-3-fluorophenyl)pyridine-2-carboxamide with cooling with ice, and the reaction liquid was stirred at the same temperature for 15 minutes. The reaction liquid was cooled to −78° C., and 1.53 ml of n-butyllithium (2.66 M hexane solution) was dropwise added to it, and the reaction liquid was stirred at the same temperature for 30 minutes. 0.36 ml of 3-methylenedihydrofuran-2 (3H)-one was added to the reaction liquid at the same temperature, and the reaction liquid was stirred at the same temperature for 2 hours, and then heated up to 0° C., and stirred for 30 minutes. Aqueous saturated sodium bicarbonate was added to the reaction temperature at the same temperature, extracted with ethyl acetate, and the organic layer was washed with saturated saline, and dried with anhydrous sodium sulfate. The solvent was evaporated away under reduced pressure, and the resulting residue was purified through silica gel column chromatography (developing solvent: hexane/ethyl acetate=3/1) to obtain the entitled compound as a colorless oily substance.

Workup

  1. temperaturewith cooling with ice
  2. customthe reaction liquid
  3. customThe reaction liquid
  4. customthe reaction liquid
  5. stirringwas stirred at the same temperature for 30 minutes
  6. customthe reaction liquid
  7. stirringwas stirred at the same temperature for 2 hours
  8. temperatureheated up to 0° C.
  9. stirringstirred for 30 minutes
  10. extractionextracted with ethyl acetate
  11. washthe organic layer was washed with saturated saline
  12. dry with materialdried with anhydrous sodium sulfate
  13. customThe solvent was evaporated away under reduced pressure
  14. customthe resulting residue was purified through silica gel column chromatography (developing solvent: hexane/ethyl acetate=3/1)
  15. customto obtain the entitled compound as a colorless oily substance

Sources & evidence

ORD record
ord-dfca0a31032d47d1aa7ce91bbc83d851
Source dataset
uspto-grants-2010_06
Patent number
US07728025B2

Linked notes

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