Ethyl 2-hydroxy-4 -phenylbutanoate

Chadha et al, have published a series of papers on the deracemization of P-hydroxyesters using whole cells of Candida parapsilosis. For example, deracemization of racemic ethyl 2-hydroxy-4-phenylbutanoic acid (22 R = H) yielded the (S) enantiomer in 85-90% yield and >99% ee (Figure 5.15) [26]. 

Using the same technique, the hydrolytic resolution of racemic frans-ethyl-2-hydroxy-4-phenylbutanoate (mc-60. Scheme 19), an important intermediate for the synthesis of antihypertension drugs such as Enalapril (61), could be accomplished [79]. The key compound R)-60 was obtained in reasonable yield and op-... 

SCHEME 36.10. A designer-bug ased approach leading to a production of 620 gL of (S)-ethyl 2-hydroxy-4-phenylbutanoate 25 with a reaction time of less than 1 day and without external cofactor addition. 

Some workers avoid delay. Pai)adium-on-carbon was used effectively for the reductive amination of ethyl 2-oxo-4-phenyl butanoate with L-alanyl-L-proline in a synthesis of the antihyperlensive, enalapril maleate. SchifTs base formation and reduction were carried out in a single step as Schiff bases of a-amino acids and esters are known to be susceptible to racemization. To a solution of 4,54 g ethyl 2-oxO 4-phenylbutanoate and 1.86 g L-alanyl-L-proline was added 16 g 4A molecular sieve and 1.0 g 10% Pd-on-C The mixture was hydrogenated for 15 hr at room temperature and 40 psig H2. Excess a-keto ester was required as reduction to the a-hydroxy ester was a serious side reaction. The yield was 77% with a diastereomeric ratio of 62 38 (SSS RSS)((55). 

The assignment of (/ )-2,3-dihydro-2-phenylfuran rests on Jones oxidation which furnished (ft)-dihydro-5-phenyl-2(3//)-furanone [(/ )-24]80. The configuration of the corresponding S-enantiomer (obtained by yeast reduction of 4-oxo-4-phenylbutanoic acid) was established by correlation with ethyl (S)-3-hydroxy-3-phenylpropanoate (of known configuration, obtained itself by a baker s yeast reduction) by a sequence featuring an Arndt -Eistert homologization as the key step (see also p 403)19. 

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