Ethyl Acetate → 3-hexyl-6-[3-(1H-imidazol-5-yl)phenyl]-6-methyl-3-azabicyclo[3.1.0]hexane

HRID 1826358Notes

Reaction equation

HRID 1826358 reaction equation
[CH2:1]([N:7]1[CH2:12][CH:11]2[CH:9]([C:10]2([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([C:20]3[NH:24][CH:23]=[N:22][CH:21]=3)[CH:15]=2)[CH3:13])[C:8]1=O)[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].[H-].[Al+3].[Li+].[H-].[H-].[H-].C(OCC)(=O)C.C(=O)([O-])O.[Na+]>O1CCCC1.[OH-].[Na+]>[CH2:1]([N:7]1[CH2:12][CH:11]2[CH:9]([C:10]2([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([C:20]3[NH:24][CH:23]=[N:22][CH:21]=3)[CH:15]=2)[CH3:13])[CH2:8]1)[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 516892Sodium BicarbonateHCID 21226445Aluminium lithium hydrideHCID 221412213-hexyl-6-[3-(1H-imidazol-5-yl)phenyl]-6-methyl-3-azabicyclo[3.1.0]hexan-2-one

Product 1

HCID 221412613-hexyl-6-[3-(1H-imidazol-5-yl)phenyl]-6-methyl-3-azabicyclo[3.1.0]hexaneYield 75%

Reagents, catalysts & solvents 2

HCID 14798Sodium HydroxideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-hexyl-6-[3-(1H-imidazol-5-yl)phenyl]-6-methyl-3-azabicyclo[3.1.0]hexan-2-one (Preparation 75, 21 mg, 62.3 μmol) in tetrahydrofuran (1.5 ml) at room temperature was added lithium aluminium hydride (1.0 M in tetrahydrofuran, 0.12 ml, 0.12 mmol) over 2 min. The reaction mixture was stirred at room temperature for 30 min and then heated under reflux for 2 h before cooling to room temperature. Aqueous sodium hydroxide solution (1 M, a few drops) and excess ethyl acetate were added followed by solid sodium hydrogen carbonate. The reaction mixture was stirred rapidly for 1 h before filtering. The mother liquor was concentrated in vacuo and the crude residue was chromatographed on silica gel eluting with ethyl acetate and then ethyl acetate:methanol (80:20) to give the product as a colourless semi-solid (15 mg, 75%).

Workup

  1. temperatureheated
  2. temperatureunder reflux for 2 h
  3. temperaturebefore cooling to room temperature
  4. stirringThe reaction mixture was stirred rapidly for 1 h
  5. filtrationbefore filtering
  6. concentrationThe mother liquor was concentrated in vacuo
  7. customthe crude residue was chromatographed on silica gel eluting with ethyl acetate

Sources & evidence

ORD record
ord-35f9f5e43033470388b0390bb4139103
Source dataset
uspto-grants-2006_05
Patent number
US07049444B2

Reaction notes

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