Réaction #6473

Équation de réaction

sodium hydroxide

methylene chloride

water

sertraline mandelate

→

Sertraline Hydrochloride

Solvants

isopropanol

Conditions de réaction

Traitement

1. 1
   AutreTo a 12 liter, 3 neck round-bottom flask equipped with mechanical stirrer
2. 2
   Autrethe resulting two clear layers were separated
3. 3
   ExtractionThe aqueous layer was further extracted with 2×586ml of methylene chloride
4. 4
   LavageThe combined methylene chloride layers were washed with 2×1110ml water
5. 5
   Autreseparated
6. 6
   workup.DISTILLATIONThe methylene chloride solution was atmospherically distilled
7. 7
   workup.ADDITION53.7ml water were added to the resulting isopropanol solution
8. 8
   workup.ADDITIONHydrogen chloride, 208.1ml of 6.37 molar, in aqueous isopropanol was added to the clear solution
9. 9
   Autreto give a thick white slurry
10. 10
    Températurecooled to room temperature overnight
11. 11
    workup.DISTILLATIONThe solution was distilled at atmospheric pressure
12. 12
    Autreto remove 1,900ml
13. 13
    workup.ADDITIONIsopropanol was then added (1000ml)
14. 14
    TempératureThe mixture was then cooled
15. 15
    Filtrationfiltered
16. 16
    Autreto yield desired crystalline polymorph (Form I)

Mode opératoire

To a 12 liter, 3 neck round-bottom flask equipped with mechanical stirrer, 4287ml of methylene chloride, 2553ml water and 638.3gms sertraline mandelate were combined. A 10% sodium hydroxide solution, 383ml, was then added and the resulting two clear layers were separated. The aqueous layer was further extracted with 2×586ml of methylene chloride. The combined methylene chloride layers were washed with 2×1110ml water and separated. The methylene chloride solution was atmospherically distilled and displaced with isopropanol to a final volume of 4440ml. 53.7ml water were added to the resulting isopropanol solution. The solution was cooled to 50° C. and seeded with sertraline hydrochloride - Form I. Hydrogen chloride, 208.1ml of 6.37 molar, in aqueous isopropanol was added to the clear solution to give a thick white slurry. Additional isopropanol 1500ml was added and the material stirred for three hours at 50° C., then cooled to room temperature overnight. The solution was distilled at atmospheric pressure to remove 1,900ml. Isopropanol was then added (1000ml) to lower the water content. The mixture was then cooled and filtered to yield desired crystalline polymorph (Form I).

Source