Hydrochloric Acid → 3-Benzyl-6-nitro-3-azabicyclo[3.1.0]hexane-2,4-dione

Participants

Reaction Conditions

Reaction Steps

A stirred mixture of 9.4 g of 4A bead molecular sieves, 9.4 g of dry Celite, (trademark), 5.62 g (30 mmol) of N-benzylmaleimide, and 120 mL of dry toluene under nitrogen was cooled to -19° C. and treated with 2.7 mL (3.9 mmol, 1.3 equivalents) of bromonitromethane. Tetrabutylammonium 2,6-di-t-butylphenoxide, the title product of Example 1, 23.38 g, was added, via a solid addition funnel, over 1.75 hours to the stirred reaction mixture at -19° C. After 15 minutes of further stirring, the reaction mixture was warmed to -1° C. and treated with 60 mL of 2N hydrochloric acid with vigorous stirring. The mixture was stirred for 1 hour and filtered through a Celite pad. The filtered solids were washed two times with 100 mL of toluene and the combined toluene solutions were washed two times with 60 mL of 2N hydrochloric acid, two times with 50 mL of water and once with brine. The resulting solution was stirred with 3.0 g of Darco (trademark) KBB overnight and filtered. The recovered Darco was washed two times with 50 mL of toluene, the toluene solutions were combined and the toluene was removed under vacuum to yield 14.95 g of a partially solidified orange-brown oil. This material was dissolved in 30 mL of toluene at 50° C. The toluene was removed by distillation under reduced pressure at 50° C., using a heated oil bath, while maintaining a constant volume by adding a total of 120 mL of isopropanol. This resulting slurry was stirred at 50° C. for 3 hours. Heating of the mixture was discontinued and the mixture was allowed to slowly cool to room temperature overnight. The mixture was then cooled to 0° C. for 3 hours and filtered. The filtered solids were washed with 10 mL of cold isopropanol followed by hexanes, and dried under vacuum giving 3.07 g (42% yield) of the title compound as a light tan solid.

Provenance & Evidence