Hydrochloric Acid → (4S)-1-[(2S,3S)-3-(N,N-Dibenzylamino)-2-hydroxy-4-phenylbutyryl]-4-chloro-N-t-butyl-L-prolinamide

12.2 g (0.04 mol) of (4S)-N-t-butoxycarbonyl-4-chloro-N-t-butyl-L-prolinamide were treated with 50 ml of a 4N solution of hydrogen chloride in dioxane, in order to remove the t-butoxycarbonyl group. The product thus obtained and 15.0 g (0.04 mol) of (2S,3S)-3-(N,N-dibenzylamino)-2-hydroxy-4-phenylbutyric acid were dissolved in 50 ml of dimethylformamide, and the solution was cooled with ice. 8.48 ml (52.0 mmol) of diethyl cyanophosphate, and then 11.2 ml (0.08 mmol) of triethylamine, were then added dropwise to the resulting mixture, which was then stirred for 1 day. At the end of this time, the reaction mixture was concentrated by evaporation under reduced pressure, and the concentrate was diluted with ethyl acetate. The diluted solution was washed with a 5% w/v aqueous solution of citric acid and with a 5% w/v aqueous solution of sodium hydrogencarbonate, in that order, after which it was dried over anhydrous sodium sulfate. The solvent was then removed by distillation under reduced pressure, and the resulting residue was purified by column chromatography, using a 1:1 by volume mixture of ethyl acetate and hexane as the eluent, to give 20.0 g of the title compound as a colorless powder, melting at 64°-67° C.

1. customto remove the t-butoxycarbonyl group
2. customThe product thus obtained
3. temperaturethe solution was cooled with ice
4. concentrationAt the end of this time, the reaction mixture was concentrated by evaporation under reduced pressure
5. additionthe concentrate was diluted with ethyl acetate
6. washThe diluted solution was washed with a 5% w/v aqueous solution of citric acid and with a 5% w/v aqueous solution of sodium hydrogencarbonate, in that order
7. dry with materialafter which it was dried over anhydrous sodium sulfate
8. customThe solvent was then removed by distillation under reduced pressure
9. customthe resulting residue was purified by column chromatography
10. additionby volume mixture of ethyl acetate and hexane as the eluent

ORDレコード

ord-75722d74621943a493c13e8214d95db2

出典データセット

uspto-grants-1997_05

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US05629406