Benzene → [1-({[4-(Benzyloxy)-2-fluorocyclohexyl]oxy}methyl)vinyl]benzene

HRID 271377Notes

Reaction equation

HRID 271377 reaction equation
[CH2:1]([O:8][CH:9]1[CH2:14][CH2:13][CH:12]([OH:15])[CH:11]([F:16])[CH2:10]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[CH:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.[C:25](=O)(O)[O-].[Na+].C(O[CH2:34][CH3:35])(=O)C>CCCCCC.O1CCCC1.CN(C)C=O>[CH2:1]([O:8][CH:9]1[CH2:14][CH2:13][CH:12]([O:15][CH2:25][C:34]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[CH2:35])[CH:11]([F:16])[CH2:10]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

9

Reactant 5

HCID 241BenzeneHCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 595431264-(Benzyloxy)-2-fluorocyclohexanol

Product 1

HCID 69275764[1-({[4-(Benzyloxy)-2-fluorocyclohexyl]oxy}methyl)vinyl]benzeneYield 25%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Conditions

Temperature
60 °C

Procedure

To a N,N-dimethylformamide (30 mL), tetrahydrofuran (30 mL) solution of 4-(Benzyloxy)-2-fluorocyclohexanol (4.28 g, 19.1 mmol) under nitrogen was added 60% sodium hydride (1.5 g, 37.5 mmol). The resulting mixture was heated at 60° C. for 0.5 h then [1-bromoethyl)vinyl]benzene [J. Am. Chem. Soc. 1954, 76, 2705.] (4.88 g, 24.8 mmol) was added. After 0.5 h the contents of the reaction flask were poured into 5% sodium bicarbonate. The resulting mixture was extracted with ethyl acetate (3×) and the combined organic extracts were washed with brine, dried with anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. Flash column chromatography (hexane:ethyl acetate, 95:5) gave [1-({[4-(Benzyloxy)-2-fluorocyclohexyl]oxy}methyl)vinyl]benzene as a pale oil (1.65 g, 25% yield): 1H NMR (CDCl3) δ 7.50-7.44 (m, 2H), 7.36-7.24 (m, 8H), 5.52 (s, 1H), 5.38 (s, 1H), 4.87-4.72 (m, 1H), 4.55-4.45 (m, 4H), 3.75-3.73 (m, 1H), 3.56-3.52 (m, 1H), 2.30-2.15 (m, 1H), 1.90-1.75 (m, 4H), 1.58-1.49 (m, 1H).

Workup

  1. extractionThe resulting mixture was extracted with ethyl acetate (3×)
  2. washthe combined organic extracts were washed with brine
  3. dry with materialdried with anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-05693aeb7a3b4214830e45f75c655a83
Source dataset
uspto-grants-2008_11
Patent number
US07452893B2

Reaction notes

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