L-Phenylalanine → phenylalaninol, (S)-

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Reaction Steps

Dry THF (1.5 L) was distilled into a 3-L three-necked flask equipped with a mechanical stirrer, a reflux condenser closed by a septum carrying nitrogen inlet and exit needles, and a stopper. Lithium aluminum hydride (38 g, 1 mole) was added cautiously through the side neck over a period of 40 min. When hydrogen evolution had subsided, the mixture was refluxed with stirring for 30 min and then cooled to room temperature. Phenylalanine (100 g) was added in small portions to the stirred suspension. The mixture was refluxed overnight and cooled to room temperature. Celite (40 g) was poured into the reaction flask, the side neck stopper was replaced by a dropping funnel, and the mixture was cooled in an ice-bath. Water (40 mL) followed by 10% w/v aqueous sodium hydroxide (40 mL) were then added dropwise with stirring. Finally, water (120 mL) was added. The mixture was filtered on a sintered filter funnel and the solid was washed with ethyl acetate (2×200 mL). Insoluble material from the filtration was replaced in the original reaction vessel and stirred for 30 min with ethyl acetate (300 mL). The mixture was filtered, and the filtrate was combined with the first filtrate, concentrated to remove THF, and diluted with ethyl acetate to about 500 mL. The solution was washed with 10% w/v aqueous sodium hydroxide and the aqueous phase was extracted with ethyl acetate (1×200 mL). The combined organic extracts were dried (MgSO4) and evaporated. The residual oil was dissolved in the minimum amount of refluxing ethyl acetate and the solution was allowed to cool to room temperature and then kept at 0° C. overnight. The first crop of product (57.2 g, after drying under oil-pump vacuum at room temperature) had mp 92°-94° C. [lit.1 mp 92°-94° C⟧ The mother liquor was evaporated and the residue was crystallized by the above procedure to furnish a second crop (5.2 g, after drying) with the same mp. The new mother liquor was processed in the same way to give a third crop (4.3 g) which was yellowish and was saved for chromatographic purification. The yield of pure (S)-phenylalaninol (crops 1 and 2) amounted to 62.4 g (68%).

Provenance & Evidence