Benzene → 3-Cyclopropylcarbonyl-1-phenyl-3-azabicyclo[3.1.0]hexane

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Reaction Steps

To a stirred slurry of 61.2 g. of 1-phenyl-1,2-cyclopropanedicarboximide (U.S. Pat. No. 3,166,571, Ex. 8) in 2 liters of benzene is added 400 ml. of Vitride® under nitrogen. The mixture is stirred at room temperature for 2 hours, refluxed for 4 hours and then stirred at room temperature for 20 hours. A 400 ml. portion of 10 N sodium hydroxide is added cautiously with stirring. The organic layer is washed twice with dilute sodium hydroxide and then with water, dried over magnesium sulfate and evaporated to give an amber oil. This oil is dissolved in dilute hydrochloric acid, washed with ether, filtered and the filtrate made basic with sodium hydroxide. The basic filtrate is extracted with benzene, dried over magnesium sulfate, filtered and evaporated to give 1-phenyl-3-azabicyclo[3.1.0]hexane as an amber oil. To a solution of 15.9 g. of 1-phenyl-3-azabicyclo[3.1.0]hexane in 100 ml. of benzene and 20 ml. of triethylamine is added 11.0 g. of cyclopropanecarboxylic acid chloride in 20 ml. of benzene over 5 minutes. The mixture is stirred for 30 minutes and 50 ml. of water is added. The benzene layer is extracted with dilute sodium bicarbonate followed by dilute hydrochloric acid and then water, dried over magnesium sulfate and evaporated to give the product 3-cyclopropylcarbonyl-1-phenyl-3-azabicyclo[3.1.0]hexane as a brown oil.

Provenance & Evidence