N,N'-Dicyclohexylurea → (2S,3aS,7aS)-1-[(2S)-2-[[(1S)-1-(Ethoxycarbonyl)butyl]amino]-1-oxopropyl]octahydro-1H-indole-2-carboxylic Acid Benzyl Ester

関与物質

反応条件

反応手順

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.

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