1,4-Dioxaspiro[4.5]decan-8-one → 8-(4-Fluorophenyl)-1,4-dioxaspiro[4.5]dec-7-ene

HRID 1173177Notes

Reaction equation

HRID 1173177 reaction equation
[CH2:1]1[O:11][C:4]2([CH2:9][CH2:8][C:7](=O)[CH2:6][CH2:5]2)[O:3][CH2:2]1.[F:12][C:13]1[CH:18]=[CH:17][C:16]([Mg]Br)=[CH:15][CH:14]=1>C1COCC1>[F:12][C:13]1[CH:18]=[CH:17][C:16]([C:7]2[CH2:8][CH2:9][C:4]3([O:11][CH2:1][CH2:2][O:3]3)[CH2:5][CH:6]=2)=[CH:15][CH:14]=1

Participants

4

Reactant 2

HCID 5674151,4-Dioxaspiro[4.5]decan-8-oneHCID 178418676HCID 178418676, compound

Product 1

HCID 152326828-(4-Fluorophenyl)-1,4-dioxaspiro[4.5]dec-7-eneYield 75%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 1,4-cyclohexanedione mono-ethylene ketal (8.1 g, 50 mmol) in THF (20 mL) at 10° C. was added a 1 M solution of 4-fluorophenyl magnesium bromide in THF (65 mL, 65 mmol). The resulting mixture was stirred at room temperature for 2 hours before quenching with saturated NH4Cl solution. The solution was extracted with EtOAc 3 times. The combined organic phase was washed with brine, dried over MgSO4 and concentrated. The residue was taken up in toluene (80 mL). To it was added p-toluenesulfonic acid monohydrate (80 mg). The mixture was stirred at reflux with removal of water using a Dean-Stark trap for 2 hours. The resulting solution was washed with saturated NaHCO3 and brine, dried over MgSO4 and concentrated. Purification on silica gel eluting with 5%, 10% and then 15% EtOAc in hexanes provided the title compound (8.8 g, 75%) as a solid. MS calculated (M+H)+ 235, found 235.

Workup

  1. custombefore quenching with saturated NH4Cl solution
  2. extractionThe solution was extracted with EtOAc 3 times
  3. washThe combined organic phase was washed with brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. additionTo it was added p-toluenesulfonic acid monohydrate (80 mg)
  7. stirringThe mixture was stirred
  8. temperatureat reflux with removal of water using a Dean-Stark trap for 2 hours
  9. washThe resulting solution was washed with saturated NaHCO3 and brine
  10. dry with materialdried over MgSO4
  11. concentrationconcentrated
  12. customPurification on silica gel eluting with 5%, 10%

Sources & evidence

ORD record
ord-be6f5f1976314b81a5b8fe990c499f44
Source dataset
uspto-grants-2010_11
Patent number
US07834021B2

Reaction notes

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