Hydrochloric Acid → HCID 86744298, compound

Participants

Reaction Steps

To a suspension of sodium borohydride (1.38 g) in tetrahydrofuran (50 ml) was added boron trifluoride etherate (4.49 ml) in a nitrogen stream with stirring at 0°~5° C. The mixture was stirred at the same condition for 30 minutes To the mixture was added a solution of (2S, 4R)-4-hydroxy-1-(4-nitrobenzyloxycarbonyl)-2-[(ureidomethylcarbonyl)aminomethyl]pyrrolidine (2.90 g) at 0°~5° C. The mixture was stirred at 0°~5° C. for 1 hour and at ambient temperature overnight. Ethanol (30 ml) was added to the reaction mixture at 0°~10° C. After stirring for 2 hours, insoluble material was filtered off and the filtrate was concentrated under reduced pressure to give a residue. A solution of the residue in a mixture of concentrated hydrochloric acid (2.9 ml) and methanol (29 ml) was stirred at ambient temperature for 20 hours. The mixture was concentrated under reduced pressure to give (2S, 4R)-4-hydroxy-1-(4-nitrobenzyloxycarbonyl)-2-[(2-ureidoethyl) aminomethyl]pyrrolidine hydrochloride. To a solution of the compound obtained above in a mixture of water (20 ml) and tetrahydrofuran (20 ml) was added a solution of 4-nitrobenzyloxycarbonyl chloride (1.60 g) in tetrahydrofuran (5 ml) under ice-cooling, keeping the pH between 8.5-9.5 with concentrated hydrochloric acid. The reaction mixture was extracted with ehtyl acetate (100 ml). The organic layer was washed with brine (50 ml×2), dried over magnesium sulfate, and concentrated under reduced pressure to give a syrup. The syrup was subjected to a column chromatography on silica gel (20 g) and eluted with a mixture of methanol and chloroform (5:95 v/v) to give (2S, 4R)-4-hydroxy-1-(4-nitrobenzyloxycarbonyl)-2-[N-(4-nitrobenzyloxycarbonyl)-N-(2-ureidoethyl)amino]methylpyrrolidine (1.78 g).

Provenance & Evidence