Hydrochloric Acid → Chloride

A solution of NaOH (0.92 g, 21.74 mmol; assay=94.52%), water (22 ml), ethanol (22 ml, technical grade, contains ˜5% 2-propanol) and Trandolapril (4.5 g, 10.39 mmol; assay=99.4%) was stirred at an internal temperature ranging from about 20° C. to about 25° C. for 19 hours. After an in process control showed an almost complete saponification (by HPLC), the reaction mixture was concentrated in vacuo to an amount of 24.42 g. This clear solution (pH=13) was slowly added to a mixture of 2N aqueous hydrochloric acid (25.22 mmol) and water (12 ml) at a temperature ranging from about 20° C. to about 25° C. within a period of 1 hour. During the addition, a sticky flocculent precipitation was observed. Afterwards, the pH of the mixture was adjusted from 2.74 to 3.84 by an addition of a few drops of 2N aqueous NaOH solution, and the mixture was stirred at a temperature ranging from about 20° C. to about 25° C. for 4 days. The suspension was then filtered off, the wet product was washed with water (15 ml) and dried in vacuo (1-5 mbar) for 15 hours at 40° C. to give Trandolaprilat in the crystalline Form D (yield: 4.07 g, 9.54 mmol, 91.8%; assay (0.1N HClO4)=96%; HPLC purity: 99.82%; water content: 4.13%, chloride content=0.15%).

1. concentrationthe reaction mixture was concentrated in vacuo to an amount of 24.42 g
2. waitranging from about 20° C. to about 25° C. within a period of 1 hour
3. additionDuring the addition
4. customa sticky flocculent precipitation
5. additionAfterwards, the pH of the mixture was adjusted from 2.74 to 3.84 by an addition of a few drops of 2N aqueous NaOH solution
6. waitranging from about 20° C. to about 25° C. for 4 days
7. filtrationThe suspension was then filtered off
8. washthe wet product was washed with water (15 ml)
9. customdried in vacuo (1-5 mbar) for 15 hours at 40° C.

ORDレコード

ord-a759685015b54bdcb750ae9841ff5dcf

出典データセット

uspto-grants-2011_05

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07943655B2