Reacción #4894

Ecuación de reacción

hydrochloric acid

sodium hydroxide

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

→

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

Disolventes

water

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturato reflux for 18 hr
2. 2
   Filtraciónthe solution filtered
3. 3
   Concentraciónconcentrated
4. 4
   Filtraciónfiltered
5. 5
   ConcentraciónThe filtrate was concentrated
6. 6
   Otrothe residue (which crystallized)
7. 7
   Temperaturawas refluxed with 300 ml of thionyl chloride for 0.5 hr
8. 8
   Concentraciónand concentrated in vacuo
9. 9
   workup.DISSOLUTIONThe residue was dissolved in 300 ml of chloroform
10. 10
    workup.DISSOLUTIONThe residue was redissolved in chloroform
11. 11
    workup.ADDITION150 ml of triethyl amine added
12. 12
    Temperaturathe mixture refluxed 1 hr
13. 13
    ConcentraciónThe solution was concentrated in vacuo
14. 14
    Otrothe residue partitioned between 400 ml of ethyl acetate, 400 ml of isopropyl ether and 500 ml of dilute hydrochloric acid
15. 15
    LavadoThe organic layer was washed twice with water and once with dilute sodium hydroxide
16. 16
    Secadodried with sodium sulfate
17. 17
    Concentraciónconcentrated
18. 18
    OtroThe residue was crystallized from isopropanol-water

Procedimiento

To 54 g (1.35 mole) of sodium hydroxide in 800 ml of water was added 148 g (0.67 mole) of 2-[(1-methyl-3-pyrrolidinyl)oxy]benzamide and the mixture brought to reflux for 18 hr. The pH was adjusted to 7 with hydrochloric acid and the solution filtered and concentrated. The residue was boiled with 400 ml of isopropanol and filtered. The filtrate was concentrated and the residue (which crystallized) was refluxed with 300 ml of thionyl chloride for 0.5 hr. and concentrated in vacuo. The residue was dissolved in 300 ml of chloroform and the solvent boiled off in vacuo. The residue was redissolved in chloroform, 150 ml of triethyl amine added and the mixture refluxed 1 hr. The solution was concentrated in vacuo and the residue partitioned between 400 ml of ethyl acetate, 400 ml of isopropyl ether and 500 ml of dilute hydrochloric acid. The organic layer was washed twice with water and once with dilute sodium hydroxide, dried with sodium sulfate and concentrated. The residue was crystallized from isopropanol-water. Yield of product was 75 g (47%), m.p. 97°-107° C.

Fuente