Ethyl Acetate → Sertraline Hydrochloride

HRID 6378

Reaction equation

HRID 6378 reaction equation
C(OCC)(=O)C.[CH3:7][NH:8][C@@H:9]1[C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=2[C@H:12]([C:19]2[CH:20]=[CH:21][C:22]([Cl:26])=[C:23]([Cl:25])[CH:24]=2)[CH2:11][CH2:10]1.C([O-])(=O)C(C1C=CC=CC=1)O.C(=O)(O)[O-].[Na+]>O>[CH3:7][NH:8][C@@H:9]1[C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=2[C@H:12]([C:19]2[CH:20]=[CH:21][C:22]([Cl:26])=[C:23]([Cl:25])[CH:24]=2)[CH2:11][CH2:10]1.[ClH:25]

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 516892Sodium Bicarbonate2×HCID 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 962WaterSolvent

Conditions

Temperature
50 °C

Procedure

To a 12 liter, 3 neck round-bottom flask equipped with mechanical stirrer, 2900ml of ethyl acetate, 2900ml water and 446.1gms of sertraline mandelate salt were combined. Sodium bicarbonate, 107 grams and 3560ml of saturated sodium bicarbonate solution were then added and the resulting two essentially clear layers were separated. The aqueous layer was further extracted with 4×740ml of ethyl acetate. The combined ethyl acetate layers were washed with 3×750ml water, 900ml of brine and separated. The ethyl acetate solution was atmospherically distilled and displaced with hexanes to a final volume of 2700ml. The solution was cooled to 50° C. and seeded with sertraline hydrochloride. Concentrated hydrochloric acid, 89.2ml, was added to the clear solution to give a thick white slurry. The mixture was then cooled, stirred overnight 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 essentially clear layers were separated
  3. extractionThe aqueous layer was further extracted with 4×740ml of ethyl acetate
  4. washThe combined ethyl acetate layers were washed with 3×750ml water, 900ml of brine
  5. customseparated
  6. distillationThe ethyl acetate solution was atmospherically distilled
  7. additionConcentrated hydrochloric acid, 89.2ml, was added to the clear solution
  8. customto give a thick white slurry
  9. temperatureThe mixture was then cooled
  10. filtrationfiltered
  11. customto yield desired crystalline polymorph (Form I)

Sources & evidence

ORD record
ord-e5eb6ae685c847db85e110fce8e7fc19
Source dataset
uspto-grants-1993_09
Patent number
US05248699

Linked notes

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