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

HRID 13392

반응식

HRID 13392 반응식
[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]

참가 물질

7

반응물 5

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

생성물 1

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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

반응 조건

온도
-78 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-dfca0a31032d47d1aa7ce91bbc83d851
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07728025B2

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