Hydrochloric Acid → Chloride

Participants

Reaction Steps

A solution of NaOH (1.84 g, 43.48 mmol; assay=94.52%), water (45 ml), ethanol (45 ml, technical grade, contains ˜5% 2-propanol) and Trandolapril (9.0 g, 20.78 mmol; assay=99.4%) was stirred at an internal temperature ranging from about 20° C. to about 25° C. for 14 hours. After an in process control showed an almost complete saponification (by HPLC), the reaction mixture was concentrated in vacuo to an amount of 64.64 g One half of the concentrated reaction mixture was used and the pH was adjusted to 3.8 by an addition of 2N aqueous hydrochloric acid (21.61 mmol) and a few drops of 2N aqueous NaOH solution. Initially during acidification, a sticky flocculent precipitation at a pH of 6 was observed, and upon further acidification a suspension containing a fine white solid was formed. The suspension was stirred at a temperature ranging from about 20° C. to about 25° C. for 16 hours and filtered off. The wet product was washed with water (30 ml) and acetone (30 ml) and dried in vacuo (1-5 mbar), 24 hours at 40° C. and 24 hours at room temperature) to give crystalline Trandolaprilat Form C (yield: 3.18 g, 7.45 mmol, 71.7% (extrapolated); assay (0.1N HClO4)=94.35%; HPLC purity=100%; water content: 5.67%, chloride content=0.16%).

Provenance & Evidence