Bromoform → HCID 22261828, compound

HRID 1610354Notes

Reaction equation

HRID 1610354 reaction equation
[F:1][C:2]([F:15])([CH:12]([F:14])[F:13])[CH2:3][O:4][C:5]1[CH:6]=[C:7]([CH3:11])[CH:8]=[CH:9][CH:10]=1.BrN1C(=O)CCC1=O.N(C(C)(C)C#N)=NC(C)(C)C#N.[F:36][C:37]1[CH:42]=[CH:41][C:40]([C:43](=[O:50])[CH2:44][C:45]([O:47][CH2:48][CH3:49])=[O:46])=[CH:39][CH:38]=1.[H-].[Na+].C(Br)(Br)Br>C(Cl)(Cl)(Cl)Cl.COCCOC.O>[F:36][C:37]1[CH:38]=[CH:39][C:40]([C:43](=[O:50])[CH:44]([CH2:11][C:7]2[CH:8]=[CH:9][CH:10]=[C:5]([O:4][CH2:3][C:2]([F:15])([F:1])[CH:12]([F:13])[F:14])[CH:6]=2)[C:45]([O:47][CH2:48][CH3:49])=[O:46])=[CH:41][CH:42]=1

Participants

10

Reactant 6

HCID 5558BromoformHCID 6547AzobisisobutyronitrileHCID 24758Sodium hydrideHCID 67184N-bromobutanimideHCID 2758844Ethyl 3-(4-Fluorophenyl)-3-OxopropanoateHCID 22261975HCID 22261975, compound

Product 1

HCID 22261828HCID 22261828, compoundYield 46.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 5943Carbon TetrachlorideSolventHCID 80711,2-DimethoxyethaneSolvent2×

Procedure

To a solution of 3-(2,2,3,3-tetrafluoropropyloxy)toluene (7.0 g, 31.5 mmol) in carbon tetrachloride (100 ml) were added N-bromosuccinimide (6.17 g, 34.7 mmol) and 2,2′-azobis(isobutyronitrile) (517 mg, 3.15 mmol) and the mixture was heated under reflux overnight. The insoluble material was filtered using celite and the filtrate was concentrated to prepare a bromo form. To a solution of ethyl 3-(4-fluorophenyl)-3-oxopropionate (5.96 g, 28.4 mmol) in 1,2-dimethoxyethane (60 ml) was added sodium hydride (60% in oil, 1.13 g, 28.4 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 the bromo form synthesized above in 1,2-dimethoxyethane (20 ml) and the reaction solution was stirred at room temperature for 1 hr. 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 (hexane:ethyl acetate=4:1) and recrystallized from diisopropyl ether-hexane to give ethyl 3-(4-fluorophenyl)-3-oxo-2-((3-(2,2,3,3-tetrafluoropropyloxy)phenyl)methyl)propionate (5.63 g, 46%).

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux overnight
  3. filtrationThe insoluble material was filtered
  4. concentrationthe filtrate was concentrated
  5. customto prepare a bromo form
  6. temperaturecooling
  7. stirringthe reaction solution was stirred at room temperature for 1 hr
  8. extractionextracted with ethyl acetate (200 ml×2)
  9. washThe extract was washed with water and saturated brine
  10. dry with materialdried over anhydrous magnesium sulfate
  11. customevaporated under reduced pressure
  12. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1)
  13. customrecrystallized from diisopropyl ether-hexane

Sources & evidence

ORD record
ord-15ebf173c619494b826ce735b773f058
Source dataset
uspto-grants-2006_01
Patent number
US06982348B2

Reaction notes

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