Reacción #4898

Ecuación de reacción

thionyl chloride

sodium hydroxide

5-bromo-2-[(1-methyl-3-pyrrolidinyl)oxy]-benzamide

triethylamine

hydrochloric acid

→

brown solid

Rendimiento 60.2%

7-Bromo-2-(2-chloroethyl)-2,3-dihydro-4-methyl-1,4-benzoxazepine-5(4H)-one

Rendimiento 60.2%

Disolventes

water

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturathe mixture was heated
2. 2
   Temperaturaat reflux for 18 hr
3. 3
   ConcentraciónThe solution was concentrated under reduced pressure
4. 4
   FiltraciónThe mixture was filtered
5. 5
   Concentraciónthe filtrate was concentrated
6. 6
   workup.DISSOLUTIONThe residue was dissolved in chloroform and to the solution
7. 7
   TemperaturaThe mixture was heated
8. 8
   Temperaturaat reflux for 0.5 hr
9. 9
   Otrodid not exceed 25° C
10. 10
    Lavadowashed consecutively with 3N hydrochloric acid, 15% aqueous sodium hydroxide and water
11. 11
    SecadoThe chloroform layer was dried over magnesium sulfate
12. 12
    Concentraciónconcentrated under reduced pressure

Procedimiento

To a solution of 9.6 g (0.24 mole) of sodium hydroxide in 200 ml of water was added 37 g (0.12 mole) of 5-bromo-2-[(1-methyl-3-pyrrolidinyl)oxy]-benzamide and the mixture was heated at reflux for 18 hr. The pH of the mixture was adjusted to 6.7 with concentrated hydrochloric acid solution. The solution was concentrated under reduced pressure and the residue was boiled in 250 ml of isopropyl alcohol for 1 hr. The mixture was filtered and the filtrate was concentrated. The residue was dissolved in chloroform and to the solution was added 28.3 g (0.24 mole) of thionyl chloride. The mixture was heated at reflux for 0.5 hr and cooled to 15° C. with an ice bath. To the mixture was added dropwise 26.6 g (0.26 mole) of triethylamine at such a rate that the temperature did not exceed 25° C. The reaction mixture was stirred at room temperature for 1 hr, then washed consecutively with 3N hydrochloric acid, 15% aqueous sodium hydroxide and water. The chloroform layer was dried over magnesium sulfate and concentrated under reduced pressure to give 23 g (60%) of brown solid. A portion of the solid was recrystallized from ethyl acetate-isopropyl ether, m.p. 92°-94° C.

Fuente