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

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.

1. temperaturethe mixture was heated
2. temperatureunder reflux for another 4 hours
3. customthe resulting precipitate was collected on
4. filtrationa filter
5. washwashed with 20 ml of diethyl ether
6. concentrationThe combined filtrates were concentrated under reduced pressure
7. distillationDibenzylformamide and unidentified compounds were distilled off from the residue under reduced pressure 1.3×10-4 mbar, bath temperature 150° C.)
8. distillationFurther distillation (bath temperature 180-200° C.)

ORDレコード

ord-191d90c4bfa845278074f40ed5e4931c

出典データセット

uspto-grants-2000_03

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US06043393