Dicyclohexylcarbodiimide → (3S-trans)-3-[[[[(4-Ethyl-2,3-dioxo-1-piperazinyl)carbonyl]amino]phenylacetyl]amino]-4-methyl-1-(phenylmethoxy)-2-azetidinone

Participants

Reaction Steps

A suspension of α-[[(4-ethyl-2,3-dioxo-1-piperazinyl)carbonyl]amino]benzeneacetic acid (0.879 g) hydroxybenzotriazole (0.42 g), and dicyclohexylcarbodiimide (0.56 g), in dimethylformamide (15 ml) is stirred at 26° C. for one hour, at which point a solution of (3S-trans)-3-amino-4-methyl-1-(phenylmethoxy)-2-azetidinone, toluenesulfonate (0.95 g) and diisopropylethylamine (0.44 ml) in dimethylformamide (5 ml) is added. The reaction mixture is stirred at room temperature for about 16 hours, then poured into water (100 ml) and extracted with ethyl acetate (three 100 ml portions). The combined organic extracts are washed with water (three 100 ml portions) and aqueous sodium bicarbonate solution (one 100 ml portion), then dried over sodium sulfate and concentrated under reduced pressure to a semi-solid residue. Liquid chromatography (ethyl acetate) affords the desired product as a foam (0.599 g). Recrystallization from chloroform/isopropyl ether yields the title compound, melting point 100°-105° C.

Provenance & Evidence