Water → Sertraline Hydrochloride

HRID 6377

Reaction equation

HRID 6377 reaction equation
C(Cl)[Cl:2].O.[CH3:5][NH:6][C@@H:7]1[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[C@H:10]([C:17]2[CH:18]=[CH:19][C:20]([Cl:24])=[C:21]([Cl:23])[CH:22]=2)[CH2:9][CH2:8]1.C([O-])(=O)C(C1C=CC=CC=1)O.[OH-].[Na+]>C(O)(C)C>[CH3:5][NH:6][C@@H:7]1[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[C@H:10]([C:17]2[CH:18]=[CH:19][C:20]([Cl:24])=[C:21]([Cl:23])[CH:22]=2)[CH2:9][CH2:8]1.[ClH:2]

Participants

6

Reactant 4

HCID 962WaterHCID 6344DichloromethaneHCID 14798Sodium HydroxideHCID 131718189(1S,4S)-4-(3,4-dichlorophenyl)-N-methyl-1,2,3,4-tetrahydronaphthalen-1-amine;2-hydroxy-2-phenylacetate

Product 1

HCID 63009Sertraline Hydrochloride

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
50 °C

Procedure

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).

Workup

  1. customTo a 12 liter, 3 neck round-bottom flask equipped with mechanical stirrer
  2. customthe resulting two clear layers were separated
  3. extractionThe aqueous layer was further extracted with 2×586ml of methylene chloride
  4. washThe combined methylene chloride layers were washed with 2×1110ml water
  5. customseparated
  6. distillationThe methylene chloride solution was atmospherically distilled
  7. addition53.7ml water were added to the resulting isopropanol solution
  8. additionHydrogen chloride, 208.1ml of 6.37 molar, in aqueous isopropanol was added to the clear solution
  9. customto give a thick white slurry
  10. temperaturecooled to room temperature overnight
  11. distillationThe solution was distilled at atmospheric pressure
  12. customto remove 1,900ml
  13. additionIsopropanol was then added (1000ml)
  14. temperatureThe mixture was then cooled
  15. filtrationfiltered
  16. customto yield desired crystalline polymorph (Form I)

Sources & evidence

ORD record
ord-3aa3f09df1fc4b0da83e26f362069cf6
Source dataset
uspto-grants-1993_09
Patent number
US05248699

Linked notes

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