Sulfuric Acid → 3-Methoxy-2,8-dimethyl-1-oxa-8-azaspiro[4.5]decane

HRID 982339Notes

Reaction equation

HRID 982339 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].S(=O)(=O)(O)O.C(O[C:15]([N:17]1[CH2:29][CH2:28][C:20]2([O:24][CH:23]([CH3:25])[CH:22]([O:26][CH3:27])[CH2:21]2)[CH2:19][CH2:18]1)=O)C.O.O.O.O.O.O.O.O.O.O.S([O-])([O-])(=O)=O.[Na+].[Na+]>O1CCCC1.CCOCC>[NH3:17].[CH3:27][O:26][CH:22]1[CH2:21][C:20]2([CH2:28][CH2:29][N:17]([CH3:15])[CH2:18][CH2:19]2)[O:24][CH:23]1[CH3:25]

Participants

8

Reactant 4

HCID 1118Sulfuric AcidHCID 62649Sodium sulfate decahydrateHCID 148520668-Ethoxycarbonyl-3-methoxy-2-methyl-1-oxa-8-azaspiro[4,5]decaneHCID 21226445Aluminium lithium hydride

Product 2

HCID 222AmmoniaHCID 103303903-Methoxy-2,8-dimethyl-1-oxa-8-azaspiro[4.5]decaneYield 145.3%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A suspension of 1.05 g lithium aluminum hydride in 35 ml anhydrous tetrahydrofuran was cooled to 0° C., 0.92 ml of 100% sulfuric acid was added dropwise while maintaining the temperature in the range from 0 to 7° C., and the mixture was stirred for 30 minutes in the above temperature range. A tetrahydrofuran solution (7 ml) containing 711 mg 8-ethoxycarbonyl-3-methoxy-2-methyl-1-oxa-8-azaspiro[4,5]-decane was then added, and stirring was continued at that temperature for one hour. Ether (35 ml) was then added, sodium sulfate decahydrate (2.6 g) was further added in small portions, and stirring was continued for an additional one hour. The white suspension thus obtained was filtered using perlite as filter aid, and the filter cake was washed with a mixed solvent of ethanol/chloroform (1:5). The washings were joined to the filtrate, the combined solution was concentrated under reduced pressure, and the residue was dissolved in chloroform. This solution was dried over anhydrous magnesium sulfate, chloroform was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography using, as eluent, a mixed solvent of chloroform/methanol/conc. ammonia (10:1:0.1 by volume), giving 400 mg 3-methoxy-2,8-dimethyl-1-oxa-8-azaspiro[4.5]decane as oil. It was converted to hydrochloride by addition of ethanolic hydrogen chloride to its ethereal solution.

Workup

  1. temperaturewhile maintaining the temperature in the range from 0 to 7° C.
  2. additionwas then added
  3. stirringstirring
  4. waitwas continued at that temperature for one hour
  5. stirringstirring
  6. waitwas continued for an additional one hour
  7. customThe white suspension thus obtained
  8. filtrationwas filtered
  9. filtrationas filter aid
  10. washthe filter cake was washed with a mixed solvent of ethanol/chloroform (1:5)
  11. concentrationthe combined solution was concentrated under reduced pressure
  12. dissolutionthe residue was dissolved in chloroform
  13. dry with materialThis solution was dried over anhydrous magnesium sulfate, chloroform
  14. distillationwas distilled off under reduced pressure
  15. customthe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-8c6f1ebc31bd423fa2c80ea0b8c22458
Source dataset
uspto-grants-1991_02
Patent number
US04996210

Reaction notes

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