Sodium Hydroxide → 1-(4-Chlorophenyl)-3-azabicyclo[3.1.0]hexane

HRID 224275Notes

Reaction equation

HRID 224275 reaction equation
[H-].COCCO[Al+]OCCOC.[Na+].[H-].[Cl:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]2([C:28]([NH2:30])=O)[CH2:24][CH:23]2[C:25](N)=O)=[CH:18][CH:17]=1.[H-].[OH-].[Na+]>C1C=CC=CC=1.O>[Cl:15][C:16]1[CH:17]=[CH:18][C:19]([C:22]23[CH2:24][CH:23]2[CH2:25][NH:30][CH2:28]3)=[CH:20][CH:21]=1

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 166653HydrideHCID 21584525Sodium bis(2-methoxyethoxy)aluminiumhydrideHCID 23332354HCID 23332354, compound

Product 1

HCID 101303311-(4-Chlorophenyl)-3-azabicyclo[3.1.0]hexane

Reagents, catalysts & solvents 2

HCID 241BenzeneSolventHCID 962WaterSolvent

Procedure

To a stirred solution of 30 ml of sodium bis(2-methoxyethoxy)aluminum hydride (70% benzene solution) is added dropwise a solution of 4.5 g of (+)-1-(p-chlorophenyl)-1,2-cyclopropanedicarboxamide in 400 ml of benzene during a 45 minute period with stirring at room temperature under nitrogen. The clear yellow solution is heated at reflux under nitrogen for 90 minutes and stored overnight at room temperature. The excess hydride reagent is decomposed by the cautious addition of 25 ml of 5 N sodium hydroxide. The mixture is diluted with 200 ml of water and the benzene phase is removed. The aqueous phase is extracted with chloroform. The combined benzene and chloroform phases are dried over magnesium sulfate and concentrated under reduced pressure to give (+)-1-(p-chlorophenyl)-3-azabicyclo[3.1.0]hexane as a tacky yellow solid. This solid is dissolved in ethanol and acidified with 20 ml of 2.3 N ethanolic hydrogen chloride. A 200 ml volume of ether is added and crystals form. These are recrystallized from acetonitrile to give the hydrochloride as white crystals, m.p. 190°-192° C.; [α]DCH3OH =+63° C.

Workup

  1. temperatureThe clear yellow solution is heated
  2. temperatureat reflux under nitrogen for 90 minutes
  3. customthe benzene phase is removed
  4. extractionThe aqueous phase is extracted with chloroform
  5. dry with materialThe combined benzene and chloroform phases are dried over magnesium sulfate
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-7c072f3e7d654439941df1d75b4a4444
Source dataset
uspto-grants-1980_11
Patent number
US04231935

Reaction notes

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