Reaction #65388

Reaction equation

4-chlorobutyryl chloride

triethylamine

4-amino-3,4-dihydro-2,2-dimethyl-6-nitro-2H-1,4-benzoxazine

→

3,4-dihydro-2,2-dimethyl-4-(2-oxo-1-pyrrolidinyl)-6-nitro-2H-1,4-benzoxazine

Solvents

methylene chloride

water

methylene chloride

Conditions

Workup

1. 1
   Temperaturethe solution was cooled on an ice bath
2. 2
   Extractionextracted with chloroform
3. 3
   DryingThe organic layer was dried over anhydrous magnesium sulfate
4. 4
   Concentrationconcentrated under reduced pressure
5. 5
   OtherThe concentrate was crystallized from ether
6. 6
   Otherto give 0.43 g of crude crystals of 4-chloro-N-(3,4-dihydro-2,2-dimethyl-6-nitro- 2H-1,4-benzoxazin-4-yl)butyrylamide
7. 7
   OtherThe crude crystals were used without purification in the next reaction
8. 8
   workup.DISSOLUTION(4) In 8 ml of N,N-dimethylformamide was dissolved 0.41 g of the above amide
9. 9
   Temperaturethe solution was cooled on an ice bath
10. 10
    workup.ADDITIONThen, 0.14 g of potassium tert-butoxide was gradually added
11. 11
    Temperaturecooling for 1 hour
12. 12
    workup.ADDITIONafter which it was diluted with water
13. 13
    Extractionextracted with ethyl acetate
14. 14
    WashThe organic layer was washed with saturated aqueous sodium chloride solution
15. 15
    Dryingdried over anhydrous magnesium sulfate
16. 16
    Filtrationfiltered
17. 17
    ConcentrationThe filtrate was concentrated under reduced pressure
18. 18
    Othercrystallized from ether
19. 19
    OtherThe crude crystals were recrystallized from ethanol

Procedure

In 4 ml of methylene chloride was dissolved 0.35 g of 4-amino-3,4-dihydro-2,2-dimethyl-6-nitro-2H-1,4-benzoxazine and the solution was cooled on an ice bath. To this solution was added 0.16 g of triethylamine followed by dropwise addition of a solution of 0.18 ml of 4-chlorobutyryl chloride in 1.4 ml of methylene chloride. After 30 minutes, the reaction mixture was diluted with water and extracted with chloroform. The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The concentrate was crystallized from ether to give 0.43 g of crude crystals of 4-chloro-N-(3,4-dihydro-2,2-dimethyl-6-nitro- 2H-1,4-benzoxazin-4-yl)butyrylamide. The crude crystals were used without purification in the next reaction. (4) In 8 ml of N,N-dimethylformamide was dissolved 0.41 g of the above amide and the solution was cooled on an ice bath. Then, 0.14 g of potassium tert-butoxide was gradually added. The mixture was stirred with ice-cooling for 1 hour, after which it was diluted with water and extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure and crystallized from ether. The crude crystals were recrystallized from ethanol to give 0.16 g of 3,4-dihydro-2,2-dimethyl-4-(2-oxo-1-pyrrolidinyl)-6-nitro-2H-1,4-benzoxazine.

Source