n,n-Dibenzylformamide → 3-Benzyl-6-(dibenzylamino)-3-azabicyclo[3.1.0]hexane

Participants

Reaction Steps

At room temperature, a solution of methylmagnesium chloride (3.4 ml, 3 M in tetrahydrofuran) was added dropwise over a period of 10 min to a mixture of N-benzyl-3-pyrroline (1.48 g) and tetraisopropoxytitanium (2.72 ml, 9.3 mmol) tetrahydrofuran. After the solution had stirred for a further 10 min, a solution of dibenzylformamide (2.1 g) in 5 ml of tetrahydrofuran was added at room temperature over a period of 30 seconds. A solution of cyclohexylmagnesium bromide (5.2 ml, 1.95 M in diethyl ether) was then added dropwise over a period of 2 hours, and the mixture was heated under reflux for another 4 hours. The hot reaction mixture was admixed with water (5 ml) (careful, exothermic reaction), and the resulting precipitate was collected on a filter and washed with 20 ml of diethyl ether. The combined filtrates were concentrated under reduced pressure. Unreacted N-benzyl-3-pyrroline. Dibenzylformamide and unidentified compounds were distilled off from the residue under reduced pressure 1.3×10-4 mbar, bath temperature 150° C.). Further distillation (bath temperature 180-200° C.) gave 3-benzyl-6-(dibenzylamino)-3-azabicyclo[3.1.0]hexane (2.62 g, 90% pure according to 1H NMR, corresponding to a yield of 69%), contaminated by dibenzylformamide, as a slightly yellowish viscous oil.

Provenance & Evidence