Water → Ethyl 3-(2,4-difluorophenyl)-3-oxo-2-((4-(trifluoromethyl)phenyl)methyl)propionate

HRID 1610385Notes

Reaction equation

HRID 1610385 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9](=[O:16])[CH2:10][C:11]([O:13][CH2:14][CH3:15])=[O:12].[H-].[Na+].[F:19][C:20]([F:30])([F:29])[C:21]1[CH:28]=[CH:27][C:24]([CH2:25]Br)=[CH:23][CH:22]=1.O>COCCOC>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9](=[O:16])[CH:10]([CH2:25][C:24]1[CH:23]=[CH:22][C:21]([C:20]([F:19])([F:29])[F:30])=[CH:28][CH:27]=1)[C:11]([O:13][CH2:14][CH3:15])=[O:12]

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 1230621-(Bromomethyl)-4-(trifluoromethyl)benzeneHCID 2758338Ethyl 3-(2,4-difluorophenyl)-3-oxopropanoate

Product 1

HCID 22262146Ethyl 3-(2,4-difluorophenyl)-3-oxo-2-((4-(trifluoromethyl)phenyl)methyl)propionateYield 77%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent2×

Procedure

To a solution of ethyl 3-(2,4-difluorophenyl)-3-oxopropionate (9 g, 39.4 mmol) in 1,2-dimethoxyethane (50 ml) was added sodium hydride (60% in oil, 1.58 g, 39.4 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 4-trifluoromethylbenzyl bromide (9.43 g, 39.4 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-(2,4-difluorophenyl)-3-oxo-2-((4-(trifluoromethyl)phenyl)methyl)propionate (11.6 g, 77%).

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-4d3ce83feecc4f1188d773af99d58882
Source dataset
uspto-grants-2006_01
Patent number
US06982348B2

Reaction notes

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