Hydrochloric Acid → (2S,4R)-2-(2-aminoethyloxymethyl)-4-hydroxy-1-(4-nitrobenzyloxycarbonyl)pyrrolidine

Participants

Reaction Steps

To a suspension of sodium borohydride (0.30 g) in tetrahydrofuran (15 ml) was added boron trifluoride etherate (3.5 ml) in a nitrogen stream with stirring at 0°-10° C. The mixture was stirred at the same temperature for 30 minutes. To the mixture was added a solution of (2S,4R)-2-(carbamoylmethyloxymethyl)-4-hydroxy-1-(4-nitrobenzyloxycarbonyl)pyrrolidine (1.40 g) in tetrahydrofuran (3 ml) at 0°-10° C. The mixture was stirred at 0°-10° C. for 3 hours and at ambient temperature overnight. Methanol (10 ml) was added to the reaction mixture at 0°-10° C. After 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 (3 ml) and methanol (30 ml) was stirred at ambient temperature for 20 hours. The mixture was concentrated under reduced pressure to give a syrup. A solution of the syrup in ethyl acetate (30 ml) was extracted with 1N hydrochloric acid (30 ml×3). The aqueous solution was adjusted to pH 10 with aqueous sodium hydroxide and extracted with chloroform (30 ml×3). The organic solution was 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 and then 10:90 V/V) to give (2S,4R)-2-(2-aminoethyloxymethyl)-4-hydroxy-1-(4-nitrobenzyloxycarbonyl)pyrrolidine (1.13 g).

Provenance & Evidence