Reacción #1877

Ecuación de reacción

trans-1-benzyl-7-chloro-5-(2-chlorophenyl)-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepine-3-acetic acid

triethylamine

diphenylphosphoryl azide

→

[trans-1-benzyl-7-chloro-5-(2-chlorophenyl)-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepine-3-yl]methylamine hydrochloride

Disolventes

dimethylformamide

Condiciones de reacción

Tratamiento posterior

1. 1
   Otroobtained
2. 2
   Otroobtained in Reference Example 5
3. 3
   workup.ADDITIONto which was added dropwise
4. 4
   Temperaturacooling
5. 5
   workup.STIRRINGThe reaction mixture was stirred for one hour at room temperature
6. 6
   ExtracciónThe mixture was subjected to extraction with ether
7. 7
   LavadoThe organic layer was washed with water
8. 8
   Otrodried
9. 9
   Concentraciónwhich was then concentrated under reduced pressure
10. 10
    workup.DISSOLUTIONThe concentrate was dissolved in 100 ml of benzene
11. 11
    Temperaturawhich was heated for 30 minutes
12. 12
    Temperaturaunder reflux
13. 13
    ConcentraciónThe reaction mixture was concentrated under reduced pressure
14. 14
    workup.ADDITIONTo the concentrate was added 6 ml of conc. hydrochloric acid
15. 15
    Temperaturathe mixture was heated for one hour
16. 16
    Temperaturaunder reflux
17. 17
    ConcentraciónThe reaction mixture was concentrated under reduced pressure
18. 18
    workup.ADDITIONby the addition of a 5% aqueous solution of potassium carbonate
19. 19
    Extracciónfollowed by extraction with ethyl acetate
20. 20
    LavadoThe organic layer was washed with water
21. 21
    Otrodried
22. 22
    workup.DISTILLATIONthe solvent was distilled off under reduced pressure
23. 23
    workup.ADDITIONTo the residue was added an ethanol solution of 4N hydrochloric acid

Procedimiento

In 5 ml of dimethylformamide was dissolved 1.0 g of trans-1-benzyl-7-chloro-5-(2-chlorophenyl)-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepine-3-acetic acid obtained obtained in Reference Example 5. To the solution was added 0.3 ml of triethylamine, to which was added dropwise, while stirring under ice-cooling, 0.6 g of diphenylphosphoryl azide. The reaction mixture was stirred for one hour at room temperature, which was then poured into ice-water. The mixture was subjected to extraction with ether. The organic layer was washed with water and dried, which was then concentrated under reduced pressure. The concentrate was dissolved in 100 ml of benzene, which was heated for 30 minutes under reflux. The reaction mixture was concentrated under reduced pressure. To the concentrate was added 6 ml of conc. hydrochloric acid, and the mixture was heated for one hour under reflux. The reaction mixture was concentrated under reduced pressure. The concentrate was made alkaline by the addition of a 5% aqueous solution of potassium carbonate, followed by extraction with ethyl acetate. The organic layer was washed with water and dried, then the solvent was distilled off under reduced pressure. To the residue was added an ethanol solution of 4N hydrochloric acid to lead it to hydrochloride to give 0.85 g of [trans-1-benzyl-7-chloro-5-(2-chlorophenyl)-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepine-3-yl]methylamine hydrochloride as crystals, m.p. 245°-250° C.

Fuente