Reacción #65388

Ecuación de reacción

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

Disolventes

methylene chloride

water

methylene chloride

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturathe solution was cooled on an ice bath
2. 2
   Extracciónextracted with chloroform
3. 3
   SecadoThe organic layer was dried over anhydrous magnesium sulfate
4. 4
   Concentraciónconcentrated under reduced pressure
5. 5
   OtroThe concentrate was crystallized from ether
6. 6
   Otroto 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
   OtroThe 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
   Temperaturathe solution was cooled on an ice bath
10. 10
    workup.ADDITIONThen, 0.14 g of potassium tert-butoxide was gradually added
11. 11
    Temperaturacooling for 1 hour
12. 12
    workup.ADDITIONafter which it was diluted with water
13. 13
    Extracciónextracted with ethyl acetate
14. 14
    LavadoThe organic layer was washed with saturated aqueous sodium chloride solution
15. 15
    Secadodried over anhydrous magnesium sulfate
16. 16
    Filtraciónfiltered
17. 17
    ConcentraciónThe filtrate was concentrated under reduced pressure
18. 18
    Otrocrystallized from ether
19. 19
    OtroThe crude crystals were recrystallized from ethanol

Procedimiento

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.

Fuente