Reaction #4114

Reaction equation

thiomorpholine

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

sodium hydroxide

→

product

Yield 88.0%

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

Yield 88.0%

Solvents

toluene

Conditions

Workup

1. 1
   Temperaturewas heated under nitrogen
2. 2
   Otherresulted
3. 3
   TemperatureThe mixture was heated
4. 4
   Temperatureunder reflux for 3 hours
5. 5
   workup.STIRRINGAfter stirring vigorously for 15 minutes
6. 6
   Otherthe layers were separated
7. 7
   ExtractionThe aqueous phase was extracted with 300 ml of toluene
8. 8
   Washwashed once with 2N sodium hydroxide solution, twice with water
9. 9
   Dryingdried over anhydrous sodium sulfate
10. 10
    Filtrationfiltered
11. 11
    Concentrationconcentrated in vacuo
12. 12
    OtherThe residue was crystallized from 100 ml of hot methanol

Procedure

A mixture of 7.88 g (0.025 mole) of 9-bromo-1,2-dihydrobenzo[b]pyrrolo[3,2,1-jk][1,4]benzodiazepin-6-one and 1200 ml of toluene was heated under nitrogen, with stirring, until a solution resulted. Then there was added 25.8 g (0.250 mole) of thiomorpholine, followed by 14.2 g (0.075 mole) of titanium tetrachloride. The mixture was heated under reflux for 3 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, filtered, and concentrated in vacuo. The residue was crystallized from 100 ml of hot methanol to give 8.8 g (88%) of product. Recrystallization from a hot solution of dichloromethane (50 ml, charcoal) to which methanol (100 ml) was added provided the analytical sample, mp 165°-167° C.

Source