Formate → (R)-2-Hydroxy-4-phenylbutyric acid

Participants

Reaction Steps

A solution of sodium 2-oxo-4-phenyl butanoate (601 mg, 3.0 mmol) and sodium formate (0.34 g, 5 mmol) in Tris buffer (5 mM; pH adjusted to 7.5 with 2M HCl). NADH (43 mg, 0.06 mM), dithiothreitol (7.5 μl of a 1M aqueous solution), formate dehydrogenase from yeast (Boehringer; 20 mg, 10 U) and R-lactate dehydrogenase from Staphylococcus epidermidis (Sigma; 31 mg, 500 U) were added successively to the solution at room temperature under nitrogen. The mixture was stirred under nitrogen for 77 hours, with periodic addition of dilute HCl (0.5 m; 3.9 ml) to maintain the pH in the range of 7.4-7.6. After acidification to pH2 and saturation with sodium chloride, the mixture was filtered under gravity. The filtrate was subjected to a normal ethyl acetate (4×70 ml) work-up with brine wash (70 ml ) to afford (R)-2-hydroxy-4-phenyl butanoic acid (7) as an amorphous white solid (513 mg, 95%) having identical spectroscopic properties to the (S)-enantiomer (compound 14). The title compound gave a melting point of 113°-115° C. and an [α]D22 value (c=2.21, EtOH) of -8.4°. 1H-NMR and capillary GC analysis of the Mosher derivative of the corresponding methyl ether indicated that homochiral (>99% ee) product had been obtained.

Provenance & Evidence