Reaction #4166

Reaction equation

ethyl N-piperazinocarboxylate

9-bromo-1,2-dihydrobenzo[b]pyrrolo[3,2,1-jk][1,4]benzodiazepine-6-one

sodium hydroxide

→

9-Bromo-6-(4-ethoxycarbonyl-1-piperazinyl)-1,2-dihydrobenzo[b]pyrrolo[3,2,1-jk][1,4]benzodiazepine

Solvents

toluene

Conditions

Workup

1. 1
   Temperaturewas heated under nitrogen until a solution
2. 2
   Otherresulted
3. 3
   TemperatureThe mixture was heated
4. 4
   Temperatureunder reflux for three hours
5. 5
   Otherthe layers were separated
6. 6
   ExtractionThe aqueous phase was extracted with 300 ml of toluene
7. 7
   Washwashed once with 2N sodium hydroxide solution, twice with water
8. 8
   Dryingdried over anhydrous sodium sulfate
9. 9
   Concentrationconcentrated in vacuo
10. 10
    Othercrystallized
11. 11
    OtherRecrystallization from ethyl acetate
12. 12
    Othergave the analytical sample, mp 128°-131° C.

Procedure

A stirred mixture of 7.88 g (0.025 mole) of 9-bromo-1,2-dihydrobenzo[b]pyrrolo[3,2,1-jk][1,4]benzodiazepine-6-one and 1200 ml toluene was heated under nitrogen until a solution resulted. Then there was added 39.6 g (0.250 mole) of ethyl N-piperazinocarboxylate followed by 14.2 g (0.075 mole) of titanium tetrachloride. The mixture was heated under reflux for three hours, cooled to room temperature and treated with 500 ml of 2N sodium hydroxide solution. After stirring vigorously for 15 minutes, the layers were separated. The aqueous phase was extracted with 300 ml of toluene. The toluene layers were combined, washed once with 2N sodium hydroxide solution, twice with water, dried over anhydrous sodium sulfate, and concentrated in vacuo. The residue was taken up in 25 ml of hot methanol from which 8.5 g (75%) of product crystallized. Recrystallization from ethyl acetate gave the analytical sample, mp 128°-131° C.

Source