Ethyl Acetate → N-[(9H-fluoren-9-yl-methoxycarbonylamino)-methyl]-2,3-dihydroxy-succinamic acid

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Reaction Steps

To Compound 32 (1.50 g, 5.06 mmol), ethyl acetate (15 ml), acetonitrile (15 ml), H2O (15 ml) and [bis(trifluoro-acetoxy)iodo]benzene (2.83 g, 6.58 mmol) were added; this was followed by stirring at room temperature for 1.5 hours. After reverse extraction was conducted using a 0.2N aqueous solution of hydrochloric acid, the water phase obtained was washed with a mixed solvent of diethyl ether:hexane. Under ice cooling, the water phase was rendered alkaline with saturated aqueous sodium hydrogen carbonate, after which it was extracted with chloroform. The organic phase was washed with saturated brine, after which it was dried with magnesium sulfate, and the solid was filtered and concentrated under reduced pressure. The residue obtained was dissolved by the addition of L-(+)-tartaric acid (1.42 g, 9.45 mmol) and N,N-dimethylformamide (100 ml). Next, 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (795 mg, 4.15 mmol) was added, and this was followed by overnight stirring at room temperature. This was concentrated under reduced pressure, the residue obtained was dissolved in ethyl acetate, and the organic phase was washed with a 2N aqueous solution of citric acid. Next, reverse extraction was conducted using aqueous sodium hydrogen carbonate, after which the water phase obtained was washed with ethyl acetate. Under ice cooling, the water phase was rendered acidic with a 2N aqueous solution of citric acid, after which it was extracted with ethyl acetate. The organic phase was washed with saturated brine, after which it was dried with sodium sulfate. The solid was filtered and concentrated under reduced pressure, after which crystallization from methanol was conducted to yield the desired N-[(9H-fluoren-9-yl-methoxycarbonylamino)-methyl]-2,3-dihydroxy-succinamic acid (Compound 33; 588 mg, 29%).

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