2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-acetamide

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 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%). After reverse extraction the water phase obtained was washed with a mixed solvent of diethyl ether after which it was extracted with chloroform The organic phase was washed with saturated brine after which it was dried with magnesium sulfate the solid was filtered concentrated under reduced pressure The residue obtained this was followed by overnight stirring at room temperature This was concentrated under reduced pressure the residue obtained the organic phase was washed with a 2N aqueous solution of citric acid extraction after which the water phase obtained was washed with ethyl acetate 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 concentrated under reduced pressure after which crystallization from methanol

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 2-amino-acetamide hydrochloride (Compound 31, 10.0 g, 90.5 mmol), a 10% aqueous solution of sodium carbonate (600 ml) and acetone (250 ml) were added; next, under ice cooling, a solution of N-(9-fluorenylmethoxycarbonyloxy)succinimide (30.5 mg, 90.5 mmol) in acetone (250 ml) was added drop by drop. After stirring at room temperature for 1 hour, the mixture was concentrated under reduced pressure; the residue obtained was dissolved in ethyl acetate, the organic phase was sequentially washed with a 2N aqueous solution of citric acid, aqueous sodium hydrogen carbonate and saturated brine, after which it was dried with magnesium sulfate. The solid was filtered and concentrated under reduced pressure, after which crystallization from methanol was conducted to yield the desired 2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-acetamide (Compound 32; 27.7 g, quant). the mixture was concentrated under reduced pressure the residue obtained the organic phase was sequentially washed with a 2N aqueous solution of citric acid, aqueous sodium hydrogen carbonate and saturated brine after which it was dried with magnesium sulfate The solid was filtered concentrated under reduced pressure after which crystallization from methanol