Reacción #4899

Ecuación de reacción

sodium hydroxide

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

triethylamine

hydrochloric acid

thionyl chloride

hydrochloric acid

sodium hydroxide

→

beige colored product

Rendimiento 23.2%

2-(2-Chloroethyl)-2,3-dihydro-7-methoxy-4-methyl-1,4-benzoxazepin-5(4H)-one

Rendimiento 23.2%

Disolventes

water

water

water

water

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturathe mixture was heated
2. 2
   Temperaturaat reflux for 24 hr
3. 3
   TemperaturaThe reaction mixture was cooled
4. 4
   ConcentraciónThe mixture was concentrated under reduced pressure
5. 5
   FiltraciónThe mixture was filtered
6. 6
   Concentraciónthe filtrate was concentrated
7. 7
   workup.DISSOLUTIONThe residue was dissolved in 500 ml of chloroform and to this solution
8. 8
   TemperaturaThe mixture was heated
9. 9
   Temperaturaat reflux for 48 hr
10. 10
    Temperaturacooled with an ice/acetone bath
11. 11
    Otrodid not exceed 25° C
12. 12
    Secadofinally dried over magnesium sulfate
13. 13
    OtroThe solvent was evaporated under reduced pressure
14. 14
    Otroto give a black solid
15. 15
    OtroThe solid was purified on a silica gel column

Procedimiento

To a solution of 19.2 g (0.48 mole) of sodium hydroxide in 500 ml of water was added 60 g (0.24 mole) of 5-methoxy-2-[(1-methyl-3-pyrrolidinyl)oxy]-benzamide and the mixture was heated at reflux for 24 hr. The reaction mixture was cooled and the pH adjusted to 6.8 with concentrated hydrochloric acid. The mixture was concentrated under reduced pressure and the residue was boiled in isopropyl alcohol for 1 hour. The mixture was filtered and the filtrate was concentrated. The residue was dissolved in 500 ml of chloroform and to this solution was added 114 g (0.96 mole) of thionyl chloride. The mixture was heated at reflux for 48 hr, then cooled with an ice/acetone bath. To the mixture was added dropwise 97 g (0.96 mole) of triethylamine at such a rate that the temperature did not exceed 25° C. The reaction solution was washeed in sequence with water, 3N hydrochloric acid solution, water, 15% aqueous sodium hydroxide and water and finally dried over magnesium sulfate. The solvent was evaporated under reduced pressure to give a black solid. The solid was purified on a silica gel column using ethyl acetate as the eluting solvent to give on isolation 15 g (23%) of beige colored product, m.p. 98°-100° C.

Fuente