Ethylene Glycol → 2-Ethyl-8-methyl-1-oxa-8-azaspiro[4.5]decan-3-one

HRID 233662Notes

Reaction equation

HRID 233662 reaction equation
C(O[C:4]([N:6]1[CH2:18][CH2:17][C:9]2([O:13][CH:12]([CH2:14][CH3:15])[C:11](=[O:16])[CH2:10]2)[CH2:8][CH2:7]1)=O)C.C(O)CO.COCCO[AlH2-]OCCOC.[Na+].C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.C1COCC1.C1(C)C=CC(S(O)(=O)=O)=CC=1.O>[CH2:14]([CH:12]1[C:11](=[O:16])[CH2:10][C:9]2([CH2:8][CH2:7][N:6]([CH3:4])[CH2:18][CH2:17]2)[O:13]1)[CH3:15]

Participants

9

Reactant 4

HCID 174Ethylene GlycolHCID 10340Sodium CarbonateHCID 16684438Red-Al2×HCID 23356741Ethyl 2-ethyl-3-oxo-1-oxa-8-azaspiro[4.5]decane-8-carboxylate

Product 1

HCID 1255222-Ethyl-8-methyl-1-oxa-8-azaspiro[4.5]decan-3-oneYield 80.3%

Reagents, catalysts & solvents 4

HCID 6101p-Toluenesulfonic acidCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

The crude 2-ethyl ketone (18.7 g) from step (a) was dissolved in 350 ml of toluene under a nitrogen atmosphere. Ethylene glycol (35 ml) and p-toluenesulfonic acid (0.75 g) were added and the reaction was heated at reflux. A Dean & Stark apparatus was used to remove the water. After 3 hrs. the reaction was cooled with an ice-bath and the toluene layer was washed with cold water. The aqueous layer was back extracted with chloroform and the combined organic layers were dried and evaporated to give the crude ketal as an oil (21.5 g). The ketal (21.5 g, 0.072 mol) was dissolved in THF (220 ml) and added dropwise to Vitride (0.216 mol ) in THF (284 ml) . The reaction was stirred overnight, cooled and then water was added to decompose the complex and excess Vitride. The THF layer was separated, dried and concentrated to give the crude 8-methyl-ketal (20.8 g). A portion of the ketal (18.8 g, 0.078 mol) was heated with 125 ml of 1.25N.HCL at 50° C. for 3 hrs. The cooled solution was neutralized with saturated Na2CO3 solution. The aqueous mixture was extracted twice with chloroform, the chloroform layer was dried and concentrated to give the title ketone as an oil (11.6 g).

Workup

  1. temperaturethe reaction was heated
  2. temperatureat reflux
  3. customto remove the water
  4. temperaturethe reaction was cooled with an ice-bath
  5. washthe toluene layer was washed with cold water
  6. extractionThe aqueous layer was back extracted with chloroform
  7. customthe combined organic layers were dried
  8. customevaporated
  9. customto give the crude ketal as an oil (21.5 g)
  10. temperaturecooled
  11. customThe THF layer was separated
  12. customdried
  13. concentrationconcentrated
  14. customto give the crude 8-methyl-ketal (20.8 g)
  15. waitHCL at 50° C. for 3 hrs
  16. extractionThe aqueous mixture was extracted twice with chloroform
  17. dry with materialthe chloroform layer was dried
  18. concentrationconcentrated

Sources & evidence

ORD record
ord-d720161abb2f467e821ea43acc13e915
Source dataset
uspto-grants-1997_01
Patent number
US05594000

Reaction notes

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