Water → Ethyl 3-(4-fluorophenyl)-2-((3-fluoro-4-(trifluoromethyl)phenyl)methyl)-3-oxopropionate

HRID 1610302Notes

Reaction equation

HRID 1610302 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:15])[CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:4][CH:3]=1.[H-].[Na+].[F:18][C:19]1[CH:20]=[C:21]([CH:24]=[CH:25][C:26]=1[C:27]([F:30])([F:29])[F:28])[CH2:22]Br.O>COCCOC>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8](=[O:15])[CH:9]([CH2:22][C:21]2[CH:24]=[CH:25][C:26]([C:27]([F:28])([F:29])[F:30])=[C:19]([F:18])[CH:20]=2)[C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 27375744-(Bromomethyl)-2-fluoro-1-(trifluoromethyl)benzeneHCID 2758844Ethyl 3-(4-Fluorophenyl)-3-Oxopropanoate

Product 1

HCID 22261470Ethyl 3-(4-fluorophenyl)-2-((3-fluoro-4-(trifluoromethyl)phenyl)methyl)-3-oxopropionateYield 66.1%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent2×

Procedure

To a solution of ethyl 3-(4-fluorophenyl)-3-oxopropionate (8.9 g, 42.3 mmol) in 1,2-dimethoxyethane (50 ml) was added sodium hydride (60% in oil, 1.69 g, 42.3 mmol) under ice-cooling and the mixture was stirred at room temperature for 30 min. To the reaction solution was dropwise added a solution of 3-fluoro-4-(trifluoromethyl)benzyl bromide (9.0 g, 42.3 mmol) in 1,2-dimethoxyethane (50 ml) and the reaction solution was stirred at room temperature for 3 hrs. The reaction solution was poured into water (200 ml) and extracted with ethyl acetate (200 ml×2). The extract was washed with water and saturated brine, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (toluene:hexane=1:1-toluene) and recrystallized from diisopropyl ether-hexane to give ethyl 3-(4-fluorophenyl)-2-((3-fluoro-4-(trifluoromethyl)phenyl)methyl)-3-oxopropionate (10.8 g, 66%).

Workup

  1. temperaturecooling
  2. stirringthe reaction solution was stirred at room temperature for 3 hrs
  3. extractionextracted with ethyl acetate (200 ml×2)
  4. washThe extract was washed with water and saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customevaporated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (toluene:hexane=1:1-toluene)
  8. customrecrystallized from diisopropyl ether-hexane

Sources & evidence

ORD record
ord-876fcf2735984c1fa8ec12fa865dd2a9
Source dataset
uspto-grants-2006_01
Patent number
US06982348B2

Reaction notes

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