Reacción #4897

Ecuación de reacción

thionyl chloride

hydrochloric acid

sodium hydroxide

4-chloro-2-[(1-methyl-3-pyrrolidinyl)oxy]benzamide

→

dark-brown solid

Rendimiento 59.0%

8-Chloro-2-(2-chloroethyl)-2,3-dihydro-4-methyl-1,4-benzoxazepin-5(4H)-one

Rendimiento 59.0%

Disolventes

ethyl acetate

water

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturathe mixture was heated
2. 2
   Temperaturaat reflux for 24 hr
3. 3
   Filtraciónfiltered
4. 4
   Concentraciónthe filtrate concentrated
5. 5
   Filtraciónthe mixture filtered
6. 6
   ConcentraciónThe filtrate was concentrated
7. 7
   Temperaturaheated
8. 8
   OtroThe excess thionyl chloride was evaporated under reduced pressure
9. 9
   workup.DISSOLUTIONThe residue was dissolved in 70 ml of chloroform
10. 10
    Otrothe solvent evaporated under reduced pressure
11. 11
    workup.DISSOLUTIONThe residue was redissolved in 75 ml of chloroform
12. 12
    workup.ADDITION40 ml of triethylamine was added gradually
13. 13
    TemperaturaThe mixture was heated
14. 14
    Temperaturaat reflux for 1 hr
15. 15
    OtroThe solvent was evaporated under reduced pressure
16. 16
    Otroto give a dark-brown solid
17. 17
    Lavadothe resulting solution washed twice with 200 ml of water and twice with 250 ml of 20% sodium hydroxide
18. 18
    SecadoThe organic layer was dried over magnesium sulfate
19. 19
    Concentraciónconcentrated under reduced pressure

Procedimiento

To a solution of 10.4 g (0.26 mole) of sodium hydroxide in 150 ml of water was added 32 g (0.13 mole) of 4-chloro-2-[(1-methyl-3-pyrrolidinyl)oxy]benzamide and the mixture was heated at reflux for 24 hr. The reaction mixture was adjusted to pH 6 with concentrated hydrochloric acid and filtered and the filtrate concentrated. The residue was boiled with 100 ml of isopropyl alcohol and the mixture filtered. The filtrate was concentrated and heated at reflux with 98 g (b 0.83 mole) of thionyl chloride for 1 hr. The excess thionyl chloride was evaporated under reduced pressure. The residue was dissolved in 70 ml of chloroform and the solvent evaporated under reduced pressure. The residue was redissolved in 75 ml of chloroform and 40 ml of triethylamine was added gradually. The mixture was heated at reflux for 1 hr. The solvent was evaporated under reduced pressure to give a dark-brown solid. The solid was dissolved in ethyl acetate and the resulting solution washed twice with 200 ml of water and twice with 250 ml of 20% sodium hydroxide. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure to give 21 g (59%) of dark-brown solid. The solid was recrystallized from isopropyl alcohol to give the title compound, m.p. 85°-87° C.

Fuente