Ammonium Chloride → 8-(3,5-Difluorophenyl)-1,4-dioxaspiro[4.5]decane

HRID 1358902Notes

Reaction equation

HRID 1358902 reaction equation
[Mg].Br[C:3]1[CH:8]=[C:7]([F:9])[CH:6]=[C:5]([F:10])[CH:4]=1.[CH2:11]1[O:21][C:14]2([CH2:19][CH2:18][CH2:17][CH2:16][C:15]2=O)[O:13][CH2:12]1.[Cl-].[NH4+]>C1COCC1.C(O)C.[Pd]>[CH2:11]1[O:21][C:14]2([CH2:19][CH2:18][CH:17]([C:3]3[CH:8]=[C:7]([F:9])[CH:6]=[C:5]([F:10])[CH:4]=3)[CH2:16][CH2:15]2)[O:13][CH2:12]1

Participants

8

Reactant 4

HCID 25517Ammonium ChlorideHCID 1363131-Bromo-3,5-difluorobenzeneHCID 5462224MagnesiumHCID 123480741,4-Dioxaspiro[4.5]decan-6-one

Product 1

HCID 206101618-(3,5-Difluorophenyl)-1,4-dioxaspiro[4.5]decaneYield 55%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A Grignard reagent prepared from dried magnesium and 50 g (0.26 mol) of 1-bromo-3,5-diflorobenzene in THF was added dropwide at room temperature to a solution of 34 g (0.22 mol) of cyclohexanedion monoethylene ketal in 500 ml of THF and the mixture was stirred for 5 hours. The reaction solution was added to 500 ml of a saturated ammonium chloride and the mixture was stirred. The reaction product was extracted with ether. The extract was dried over magnesium sulfate and the solvent was distilled off. The residue and 2 g of p-toluenesulfonic acid were added to 300 ml of toluene, and the mixture was refluxed for 3 hours, while removing the produced water using Dean-Stark. The reaction solution was washed successively with water, a saturated aqueous sodium carbonate and water, dried over magnesium sulfate, and then the solvent was distilled off. The residue was purified by column chromatography on silica gel (eluting solvent: heptane/ethyl acetate=3/1), and the solvent was distilled off under reduced pressure. The residue thus obtained was hydrogenated in ethanol in the presence of 2 g of 5% palladium/carbon. The catalyst was filtered off and then the solvent was distilled off to afford 31 g (0.12 mol) of 4-(3,5-difluorophenyl)-cyclohexanone mono-ethylene ketal.

Workup

  1. stirringthe mixture was stirred
  2. extractionThe reaction product was extracted with ether
  3. dry with materialThe extract was dried over magnesium sulfate
  4. distillationthe solvent was distilled off
  5. additionThe residue and 2 g of p-toluenesulfonic acid were added to 300 ml of toluene
  6. temperaturethe mixture was refluxed for 3 hours
  7. customwhile removing the produced water using Dean-Stark
  8. washThe reaction solution was washed successively with water
  9. dry with materiala saturated aqueous sodium carbonate and water, dried over magnesium sulfate
  10. distillationthe solvent was distilled off
  11. customThe residue was purified by column chromatography on silica gel (eluting solvent: heptane/ethyl acetate=3/1)
  12. distillationthe solvent was distilled off under reduced pressure
  13. customThe residue thus obtained
  14. filtrationThe catalyst was filtered off
  15. distillationthe solvent was distilled off

Sources & evidence

ORD record
ord-a218f8ff88534adbb87260b4c963e2f3
Source dataset
uspto-grants-2003_07
Patent number
US06599590B2

Reaction notes

Loading…