L-Hydroxyproline → (2S,4R)-1-[(9H-fluoren-9-ylmethoxy)carbonyl]-4-hydroxypyrrolidine-2-carboxylic acid

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Reaction Steps

Hydroxyproline (5.0 g, 38.2 mmol) and sodium bicarbonate (8.0 g, 95.2 mmol) were suspended in 150 mL of water:dioxane (1:1). Fluorenylmethyl chloroformate (11.4 g, 44.0 mmol) in 25 mL of toluene was added dropwise. The temperature of the reaction was not allowed to rise above 25° C. during the addition. The mixture was stirred vigorously overnight, and then quenched with saturated sodium bicarbonate (50 mL) and water (50 mL). The solution was then extracted with diethyl ether (100 mL). The aqueous layer was acidified to pH 1 with concentrated HCl and extracted twice with ethyl acetate. The organic extracts were washed with brine. The solution was then dried with anhydrous magnesium sulfate, filtered and the solvent removed in vacuo. After crystallization, 13.4 g (100%) of pure N-Fmoc-trans-4-hydroxy-L-proline was obtained.

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