反应详情

温度

25 °C

Triethyl amine (14 g, 0.1238 moles) was added to a suspension of (2S,3aS,7aS)-octahydroindole-2-carboxylic acid-benzyl ester para toluene sulfonate (20 g, 0.0464 moles) in ethyl acetate (240 g), under stirring at 25° C. in one lot. Then 1-hydroxybenzotriazole (24 g, 0.1776 moles), N-[(S)-1-carbethoxybutyl]-(S)-alanine (30 g, 0.1382 moles) were added to the reaction mixture at 25° C., under stirring, followed by dicyclohexyl carbodiimide (28 g, 0.1357 moles) at ambient temperature. The reaction mixture was stirred, keeping the temperature in the range of 15-20° C. for 3 hrs, when the TLC and the HPLC indicated a completion of the reaction. The reaction mixture was then filtered to remove the precipitated dicyclohexyl urea. The filtrate was washed with water (100 ml, twice). The organic layer was dried over sodium sulphate and concentrated under reduced pressure to afford a viscous oil, which was still contaminated with dicyclohexyl urea. The oil was redissolved in ethyl acetate (100 ml) and the solution was cooled to 2-5° C. under stirring for 1 hr. The precipitated dicyclohexyl urea was again filtered off and the filtrate was concentrated under reduced pressure to afford 20 g (94%) of perindopril benzyl ester as an oil.

1. stirringunder stirring
2. stirringThe reaction mixture was stirred
3. customin the range of 15-20° C.
4. customfor 3 hrs
5. customa completion of the reaction
6. filtrationThe reaction mixture was then filtered
7. customto remove the precipitated dicyclohexyl urea
8. washThe filtrate was washed with water (100 ml
9. dry with materialThe organic layer was dried over sodium sulphate
10. concentrationconcentrated under reduced pressure
11. customto afford a viscous oil, which
12. temperaturethe solution was cooled to 2-5° C.
13. stirringunder stirring for 1 hr
14. filtrationThe precipitated dicyclohexyl urea was again filtered off
15. concentrationthe filtrate was concentrated under reduced pressure