Sodium hydride → 1-(4'-Ethoxy-2',3'-Difluorophenyl)methyloxy-2,3,3-Trifluoro-4-n-Propyl bicyclo[2.2.2]octane

HRID 1644126Notes

Reaction equation

HRID 1644126 reaction equation
[F:1][CH:2]1[C:7]([F:9])([F:8])[C:6]2([CH2:12][CH2:13][CH3:14])[CH2:10][CH2:11][C:3]1([OH:15])[CH2:4][CH2:5]2.Br[CH2:17][C:18]1[CH:23]=[CH:22][C:21]([O:24][CH2:25][CH3:26])=[C:20]([F:27])[C:19]=1[F:28].[H-].[Na+].[Cl-].[NH4+]>CN(C)C=O>[CH2:25]([O:24][C:21]1[CH:22]=[CH:23][C:18]([CH2:17][O:15][C:3]23[CH2:11][CH2:10][C:6]([CH2:12][CH2:13][CH3:14])([CH2:5][CH2:4]2)[C:7]([F:8])([F:9])[CH:2]3[F:1])=[C:19]([F:28])[C:20]=1[F:27])[CH3:26]

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 229135944-Ethoxy-2,3-difluorobenzyl bromideHCID 594808822,3,3-Trifluoro-1-Hydroxy-4-n-Propylbicyclo[2.2.2]octane

Product 1

HCID 594809851-(4'-Ethoxy-2',3'-Difluorophenyl)methyloxy-2,3,3-Trifluoro-4-n-Propyl bicyclo[2.2.2]octane

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2,3,3-Trifluoro-1-hydroxy-4-n-propylbicyclo[2.2.2]octane (4) (37.5 mg), and 4-bromomethyl-1-ethoxy-2,3-difluorobenzene (5) (65.4 mg) were added to a dimethyl formamide suspension (2.0 mL) of sodium hydride (4.9 mg), the mixture was stirred at room temperature for 2.5 hours, and then added with saturated aqueous ammonium chloride solution to thereby terminate the reaction. The organic layer was extracted three times with ethyl acetate, the organic layers were combined, and washed with saturated sodium chloride solution. The organic layer was dried over anhydrous sodium sulfate, and the solvent was then vaporized off under reduced pressure, to thereby obtain a crude product. The crude product was purified by silica gel column chromatography (hexane/ethyl acetate=9:1), to thereby obtain 1-(4′-ethoxy-2′,3′-difluorophenyl)methyloxy-2,3,3-trifluoro-4-n-propyl bicyclo[2.2.2]octane (6) (yield=39.9 mg, yield ratio=60%) as a colorless clear crystal.

Workup

  1. customto thereby terminate
  2. customthe reaction
  3. extractionThe organic layer was extracted three times with ethyl acetate
  4. washwashed with saturated sodium chloride solution
  5. dry with materialThe organic layer was dried over anhydrous sodium sulfate

Sources & evidence

ORD record
ord-84446736e48144c1921ed82f6c8ba262
Source dataset
uspto-grants-2012_02
Patent number
US08124196B2

Reaction notes

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