Water → 4-Benzyl-7-oxa-4-azaspiro[2.5]octane

HRID 584174Notes

Reaction equation

HRID 584174 reaction equation
[CH2:1]([N:8]1[C:15](=O)[CH2:14][O:13][CH2:12][C:9]21[CH2:11][CH2:10]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-].[F-].[Na+].O>O1CCCC1>[CH2:1]([N:8]1[CH2:15][CH2:14][O:13][CH2:12][C:9]21[CH2:10][CH2:11]2)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 962WaterHCID 5235Sodium FluorideHCID 21226445Aluminium lithium hydrideHCID 22342769HCID 22342769, compound

Product 1

HCID 223426924-Benzyl-7-oxa-4-azaspiro[2.5]octaneYield 51.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
50 °C

Procedure

A solution of 4-benzyl-5-oxo-7-oxa-4-azaspiro[2.5]octane (695.3 mg) in tetrahydrofuran (8 ml) was added dropwise to an ice-cooled suspension of lithium aluminum hydride (112 mg) in tetrahydrofuran (5 ml) over 20 minutes and then the mixture was stirred at 50° C. for 2 hours under nitrogen atmosphere. After being cooled to room temperature, sodium fluoride (495 mg) was added to the mixture. The mixture was stirred vigorously and cooled with ice-bath. Water (0.16 ml) was added thereto and the mixture was filtered. The filtrate was concentrated under reduced pressure to give an oil. The oil was purified by column chromatography on silica gel using a mixture of hexane and ethyl acetate as eluent to give 4-benzyl-7-oxa-4-azaspiro[2.5]octane (334.8 mg). 4-Benzyl-7-oxa-4-azaspiro[2.5]octane in ethanol (8 ml) was hydrogenated over palladium hydroxide on carbon for 2 hours at atmospheric pressure. After removal of the catalyst by filtration, the filtrate was treated with 4N hydrogen chloride in ethyl acetate (2 ml) and concentrated under reduced pressure to give 7-oxa-4-azaspiro[2.5]octane hydrochloride (81 mg).

Workup

  1. temperaturecooled
  2. temperatureAfter being cooled to room temperature
  3. stirringThe mixture was stirred vigorously
  4. temperaturecooled with ice-bath
  5. filtrationthe mixture was filtered
  6. concentrationThe filtrate was concentrated under reduced pressure
  7. customto give an oil
  8. customThe oil was purified by column chromatography on silica gel using
  9. additiona mixture of hexane and ethyl acetate as eluent

Sources & evidence

ORD record
ord-9033eb218b8f4423bf0eb676116400d5
Source dataset
uspto-grants-2005_08
Patent number
US06924278B2

Reaction notes

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