Thionyl Chloride → HCID 178501871, compound

Participants

Reaction Conditions

Reaction Steps

A solution of (1R)-(+)-(1-benzyloxycarbonylamino-2-methylpropyl)phosphonic acid (4.27 g, 14.9 mmol) in 50 mL of DMF was cooled to −20° C. using a dry ice/methanol bath. To this was added thionyl chloride (1.20 mL, 16.5 mmol) and the reaction mixture was stirred at −5° C. for 40 minutes. 2-(3-(N′,N″-Di(t-butoxycarbonyl)guanidino)phenyl)-2-hydroxyethanoic acid methyl ester (5.60 g, 13.2 mmol) was added to the reaction mixture as a solution in 15 mL of DMF and the reaction was allowed to warm to ambient temperature. After stirring for 3 days, 20 mL of saturated NaHCO3 was added. The solution was washed with ether (2×), combined and concentrated in vacuo to give a mixture of product and starting material. The product was purified by flash column chromatography (10%-100% ethyl acetate/methylene chloride), followed by methanol to give 5.07 g (55%) of 2-(3-(N′,N″-di(t-butoxycarbonyl)guanidino)phenyl)-2-((1R)-(1-(benzyloxycarbonyl)amino-2-methylpropyl)(hydroxy)phosphinoyloxy)ethanoic acid methyl ester.

Provenance & Evidence