Ethyl Acetate → Sertraline Hydrochloride

Participants

Reaction Conditions

Reaction Steps

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).

Provenance & Evidence