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

HRID 1446473

Reaction equation

HRID 1446473 reaction equation
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]

Participants

7

Reactant 4

HCID 8028Tetrahydrofuran2×HCID 12702Diethyl fluoromalonateHCID 24758Sodium hydrideHCID 66961330(E)-3-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl)acrylic acid ethyl ester

Product 1

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

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-f634e7961eb04331a5a3b9591124e43a
Source dataset
uspto-grants-2010_02
Patent number
US07667041B2

Linked notes

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