Phosphate → Ethyl (R)-2-hydroxy-4-phenylbutyrate

참여 물질

반응 단계

A 3 L three-neck, round-bottom flask equipped with a mechanical stirrer, an electrode connected to a pH control unit and an addition tube connected to a peristaltic pump, was charged with 450 ml of deionized water, 50 ml of 0.05M aqueous phosphate buffer (pH 7.0) and 52.0 g of racemic ethyl 2-hydroxy-4-phenylbutanoate. The mixture was stirred for several minutes to make certain that the pH remained constant at 7.0. Then, 0.67 g (20,000 units) of Pseudomonas lipase enzyme (P-30, Amano International Enzyme Co., Inc., Troy, Va.) was added and the hydrolysis was allowed to proceed at pH 7.0 and room temperature, with stirring. The pH was kept constant by adding 1.0N aqueous sodium hydroxide solution via the peristaltic pump, which was activated by the pH control unit. The reaction was discontinued at 50% conversion when 125 ml of 1.0N aqueous sodium hydroxide solution had been added (at the 24 hour mark). The reaction mixture was then extracted with 3 portions of 200 ml (600 ml total) of diethyl ether. The combined organic layers were dried over anhydrous sodium sulfate and the solvent was removed at 45° C. under 70 mm Hg of vacuum, to provide 25.3 g of ethyl (2R)-2-hydroxy-4-phenylbutanoate (48.5% yield; 97% of theory), which was 91% enantiomerically pure (α)D25 -7.8° (c 1.0, EtOH). The aqueous layer was acidified to pH 2 with 3N hydrochloric acid and extracted with 3×200 ml of diethyl ether. The combined organic layers were dried over anhydrous sodium sulfate and the solvent was removed at 45° C. and 70 mm Hg to give 20.8 g of (2S)-2-hydroxy-4-phenylbutanoic acid (46% yield; 92% of theory), which was 90.8% enantiomerically pure. (α)D25 +7.6° (c 1.0, EtOH), m.p. 109°-110° C.

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