Toluene → tert-butyl (2S)-2-amino-3-phenylpropanoate

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Reaction Steps

The benzaldehyde Schiff base of glycine tert-butyl ester (compound 9) (0.44 g; 2 mmol), benzyl bromide (0.32 g; 1.9 mmol), and N-(9-anthracenylmethyl)cinchonidium chloride (compound 10) (107 mg; 0.2 mmol) were added to toluene (4 mL), and the mixture was stirred vigorously (1400 rpm) with ice-salt cooling. When the internal temperature thereof had dropped to −5° C. or less, 48% KOH aqueous solution (0.46 g; 4 mmol, 2 equivalents) was added thereto. The mixture was stirred for one hour while maintaining the internal temperature between −5° C. and −2° C. Distilled water (10 mL) was added thereto and the toluene layer was collected, and then the alkylated Schiff base (compound 11) was extracted with toluene (10 mL×2). Thus obtained toluene layers were combined with the toluene layer collected previously, 1 N hydrochloric acid (10 mL) was added thereto, and the mixture was stirred at room temperature for one hour. The aqueous layer was collected by separation, and then the aqueous layer was washed with toluene (10 mL), and sodium carbonate was added thereto carefully to avoid too vigorous bubbling until pH of the solution reached not lower than 11 (confirmed by universal pH test paper). The mixture was extracted with ethyl acetate (10 mL×3) to collect the ethyl acetate layer. The ethyl acetate layer was dried over magnesium sulfate and concentrated under reduced pressure to give (S)-phenylalanine tert-butyl ester (compound (S)-12) (0.11 g; yield 25%, optical purity 80% ee). The optical purity of the compound 12 was measured by HPLC under the following conditions:

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