Water → HCID 22342660, compound

HRID 584240Notes

Reaction equation

HRID 584240 reaction equation
[CH2:1]([N:8]1[C:13]([CH3:15])([CH3:14])[CH2:12][O:11][CH2:10][C:9]1=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-].O.[OH-].[Na+]>O1CCCC1>[CH2:1]([N:8]1[CH2:9][CH2:10][O:11][CH2:12][C:13]1([CH3:15])[CH3:14])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 962Water2×HCID 14798Sodium HydroxideHCID 21226445Aluminium lithium hydrideHCID 22342670HCID 22342670, compound

Product 1

HCID 22342660HCID 22342660, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

4-Benzyl-5,5-dimethyl-3-morpholinone (4.45 g) was added to an ice-cooled suspension of lithium aluminum hydride (0.77 g) in dried tetrahydrofuran (20 ml) under nitrogen atmosphere. After 5 hours of stirring at 50° C., the reaction mixture was cooled below 5° C., and water (0.36 ml), 12% sodium hydroxide aqueous solution (0.36 ml) and water (1 ml) were added thereto successively. After 30 minutes of stirring, the mixture was filtrated through Celite® pad, and the pad was washed with ethyl acetate. The filtrate and washing were combined and the whole was dried over magnesium sulfate, and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel using a mixture of n-hexane and ethyl acetate. The fractions containing the objective compound were collected and evaporated under reduced pressure to give 4-benzyl-3,3-dimethylmorpholine as an oil. The obtained oil and ammonium formate (5.7 g) were dissolved into a mixed solvent of ethanol (35 ml) and water (5 ml), and the whole was stirred under reflux for 1 hour under nitrogen atmosphere. After cooling, the mixture was filtrated through Celite® pad. The filtrate was evaporated under reduced pressure. The residue was dissolved into methanol and 4N hydrogen chloride in ethyl acetate solution was added-thereto. The whole mixture was evaporated and the residue was triturated with a mixture of ethanol and n-hexane (1:1). The resulting crystals were collected by filtration and washed with a mixed solvent of ethanol and n-hexane (1:1) to give colorless crystals of 3,3-dimethylmorpholine hydrochloride (1.56 g).

Workup

  1. temperaturecooled
  2. temperaturethe reaction mixture was cooled below 5° C.
  3. stirringAfter 30 minutes of stirring
  4. filtrationthe mixture was filtrated through Celite® pad
  5. washthe pad was washed with ethyl acetate
  6. washThe filtrate and washing
  7. dry with materialthe whole was dried over magnesium sulfate
  8. customevaporated under reduced pressure
  9. customThe residue was purified by column chromatography on silica gel using
  10. additiona mixture of n-hexane and ethyl acetate
  11. additionThe fractions containing the objective compound
  12. customwere collected
  13. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-8ed3ca564fd5422d85cb963e0c738e33
Source dataset
uspto-grants-2005_08
Patent number
US06924278B2

Reaction notes

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