Réaction #1552129

Équation de réaction

2-chloro-N-(4-chlorophenethyl)propan-1-amine hydrochloride

aluminum chloride

→

crude title compound

8-Chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine

Solvants

1,2-Dichlorobenzene

Conditions de réaction

Traitement

1. 1
   AutreThe resulting Friedel-Crafts reaction mixture
2. 2
   Températureis then cooled
3. 3
   AutrePurified
4. 4
   workup.ADDITIONpotable water (about 1060 kg) and silica gel are charged to a second vessel
5. 5
   AutreThe cooled Friedel-Crafts reaction mixture
6. 6
   workup.ADDITIONis then added to the aqueous silica gel slurry
7. 7
   workup.STIRRINGstirred
8. 8
   Températurecooled in the second vessel
9. 9
   AutreThe stirred quench mixture
10. 10
    Filtrationis filtered at about 58° C.
11. 11
    Filtrationthe silica gel filter cake
12. 12
    Lavageis washed
13. 13
    Autrewith purified
14. 14
    Lavageto rinse the quench vessel into the filter
15. 15
    LavageThe mother and wash liquor filtrates
16. 16
    Autreare combined in a vessel
17. 17
    Températureare cooled
18. 18
    workup.STIRRINGwith stirring to about 22° C
19. 19
    workup.STIRRINGStirring
20. 20
    Autrethree phases separate
21. 21
    workup.ADDITIONcontaining a smaller amount of the product
22. 22
    AutreThese upper two phases are partitioned between cyclohexane (about 583 kg) and enough aqueous sodium hydroxide solution, approx. 30 wt %
23. 23
    LavageThe cyclohexane phase is washed
24. 24
    Autrewith purified
25. 25
    workup.DISTILLATIONpotable water (about 1272 kg) at about 57° C. and then distilled at reduced pressure
26. 26
    Autreto remove solvent

Mode opératoire

1,2-Dichlorobenzene (about 1522 kg), 2-chloro-N-(4-chlorophenethyl)propan-1-amine hydrochloride (about 530 kg, 1.97 kmol, 1.00 eq.), and aluminum chloride (about 387 kg, 2.90 kmol, 1.47 eq.) are charged to a vessel vented to a caustic scrubber. The mixture is then stirred and heated at about 126° C. under nitrogen for about 16 h. The resulting Friedel-Crafts reaction mixture is then cooled. Purified or potable water (about 1060 kg) and silica gel are charged to a second vessel. The cooled Friedel-Crafts reaction mixture is then added to the aqueous silica gel slurry stirred and cooled in the second vessel. The stirred quench mixture is filtered at about 58° C., and the silica gel filter cake is washed with purified or potable water (about 212 kg). Optionally, some or all of this water may be used to rinse the quench vessel into the filter. The mother and wash liquor filtrates are combined in a vessel and are cooled with stirring to about 22° C. Stirring is then stopped, and upon settling, three phases separate. The brown lowest phase consists mostly of 1,2-dichlorobenzene and is drained to solvent regeneration. The lower of the remaining two phases, which is the middle phase of the original three-phase mixture, contains most of the product. The topmost phase is a turbid water phase containing a smaller amount of the product. These upper two phases are partitioned between cyclohexane (about 583 kg) and enough aqueous sodium hydroxide solution, approx. 30 wt %, to achieve an aqueous phase pH of at least about 13. The cyclohexane phase is washed with purified or potable water (about 1272 kg) at about 57° C. and then distilled at reduced pressure to remove solvent and provide crude title compound, an oil, as the distillation residue.

Source