Tetrahydrofuran → (E)-2-fluoro-3-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl)acrylic acid ethyl ester

HRID 1362618

반응식

HRID 1362618 반응식
C(O[C:4](=O)[CH:5]([F:11])[C:6]([O:8][CH2:9][CH3:10])=[O:7])C.C1COCC1.[H-].[Na+].C(OC(=O)/C=C/[C:26]1[CH:31]=[CH:30][C:29]([N:32]2[CH:36]=[C:35]([CH3:37])[N:34]=[CH:33]2)=[C:28]([O:38][CH3:39])[CH:27]=1)C>O.C(OCC)(=O)C>[CH2:9]([O:8][C:6](=[O:7])/[C:5](/[F:11])=[CH:4]\[C:26]1[CH:31]=[CH:30][C:29]([N:32]2[CH:36]=[C:35]([CH3:37])[N:34]=[CH:33]2)=[C:28]([O:38][CH3:39])[CH:27]=1)[CH3:10]

참가 물질

7

반응물 4

HCID 8028Tetrahydrofuran2회HCID 12702Diethyl fluoromalonateHCID 24758Sodium hydrideHCID 66961330(E)-3-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl)acrylic acid ethyl ester

생성물 1

HCID 66961280(E)-2-fluoro-3-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl)acrylic acid ethyl ester수율 56%

시약·촉매·용매 2

HCID 962Water용매HCID 8857Ethyl Acetate용매

실험 절차

2-fluoro malonic acid diethyl ester (670 μL) was added to a THF (8 mL) suspension of sodium hydride (170 mg) under ice-cooling, and the reaction solution was agitated under ice-cooling for 20 minutes and further agitated at room temperature for 1 hour. After dropping the THF (2 mL) solution of (E)-3-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl)acrylic acid ethyl ester (1 g) obtained above to the reaction solution over 10 minutes and the reaction solution was agitated at room temperature for 30 minutes, and heated to reflux for 8 hours. After the reaction solution was allowed to be cooled to room temperature, ethyl acetate and water was added and the organic layer was washed with a saturated ammonium chloride solution. After drying the organic layer over anhydrous magnesium sulfate, the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (Carrier: Chromatorex™ NH, elution solvent: from hexane to hexane:ethyl acetate=1:1), and 593 mg (56%) of (E)-2-fluoro-3-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl)acrylic acid ethyl ester was obtained. The physical properties of the compound are as follows.

후처리

  1. temperaturecooling
  2. temperaturecooling for 20 minutes
  3. stirringfurther agitated at room temperature for 1 hour
  4. customobtained above to the reaction solution over 10 minutes
  5. stirringthe reaction solution was agitated at room temperature for 30 minutes
  6. temperatureheated
  7. temperatureto reflux for 8 hours
  8. washthe organic layer was washed with a saturated ammonium chloride solution
  9. dry with materialAfter drying the organic layer over anhydrous magnesium sulfate
  10. customthe solvent was evaporated under reduced pressure
  11. customThe obtained residue was purified by silica gel column chromatography (Carrier: Chromatorex™ NH, elution solvent: from hexane to hexane:ethyl acetate=1:1)

출처 및 근거

ORD 기록
ord-7830f66e44cb424ca829a6c4d70d7f0f
출처 데이터셋
uspto-grants-2011_02
특허 번호
US07880009B2

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