1-Bromo-4-fluorobenzene → 8-(4-Fluorophenyl)-1,4-dioxaspiro[4.5]decan-8-ol

HRID 1019266Notes

Reaction equation

HRID 1019266 reaction equation
[Mg].Br[C:3]1[CH:8]=[CH:7][C:6]([F:9])=[CH:5][CH:4]=1.[CH2:10]1[O:20][C:13]2([CH2:18][CH2:17][C:16](=[O:19])[CH2:15][CH2:14]2)[O:12][CH2:11]1>C1COCC1>[CH2:11]1[O:12][C:13]2([CH2:18][CH2:17][C:16]([OH:19])([C:3]3[CH:8]=[CH:7][C:6]([F:9])=[CH:5][CH:4]=3)[CH2:15][CH2:14]2)[O:20][CH2:10]1

Participants

5

Reactant 3

HCID 99931-Bromo-4-fluorobenzeneHCID 5674151,4-Dioxaspiro[4.5]decan-8-oneHCID 5462224Magnesium

Product 1

HCID 152326818-(4-Fluorophenyl)-1,4-dioxaspiro[4.5]decan-8-olYield 87%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a 500 ml round-bottom flask equipped with a mechanical stirrer, condenser and addition funnel were added magnesium turnings (3.50 g, 140 mmol) and enough THF to cover the Mg. A solution of 1-bromo-4-fluorobenzene (12.45 g, 70.43 mmol) in THF (90 ml) was added dropwise at such a rate that the reaction maintained a gentle reflux following reaction-initiation (the initiation may be accomplished by warming the flask). After the mixture was refluxed for an additional 2.5 h, a solution of 1,4-cylohexanedione monoethylene ketal (10.00 g, 64.03 mmol) in THF (75 ml) was added dropwise. The mixture was kept at refluxing for an additional 2 h before being quenched with saturated ammonium chloride solution (7 ml). After removal of the magnesium salts by filtration, the filtrate was concentrated to dryness. The residue was dissolved in CHCl3 and washed with water and brine. The organic layer was separated, dried over MgSO3, and concentrated. The residue was purified by flash chromatography (30% ether in petroleum ether) to afford the desired alcohol (13.50 g, 87%) as a colorless solid. mp 133-134° C. 1H NMR (500 MHz, CDCl3) δ1.69 (d, J=11.7 Hz, 2H), 1.79 (d, J=12.2 Hz, 2H), 2.05-2.18 (m, 4H), (m, 4H), 7.02 (t, J=8.3, 2H), 7.47-7.50 (m, 2H).

Workup

  1. customTo a 500 ml round-bottom flask equipped with a mechanical stirrer, condenser and addition funnel
  2. temperaturemaintained
  3. temperaturea gentle reflux
  4. customreaction-initiation (the initiation
  5. temperatureby warming the flask)
  6. temperatureAfter the mixture was refluxed for an additional 2.5 h
  7. temperatureat refluxing for an additional 2 h
  8. custombefore being quenched with saturated ammonium chloride solution (7 ml)
  9. customAfter removal of the magnesium salts
  10. filtrationby filtration
  11. concentrationthe filtrate was concentrated to dryness
  12. dissolutionThe residue was dissolved in CHCl3
  13. washwashed with water and brine
  14. customThe organic layer was separated
  15. dry with materialdried over MgSO3
  16. concentrationconcentrated
  17. customThe residue was purified by flash chromatography (30% ether in petroleum ether)

Sources & evidence

ORD record
ord-6fa9c44917364ff0af0f962dc471d86a
Source dataset
uspto-grants-2002_11
Patent number
US06486199B1

Reaction notes

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