Synthesis of (aryl or arylalkyl)-3-hydroxy propionic acids and aryl alkanediols having high optical purity
US4921798A · kind A · utility
Assignee
Inventor
Key dates
| Filing date | Sep 25, 1989 |
| Grant date | May 1, 1990 |
| Priority date | — |
| Expiry date | Sep 25, 2009 |
Classification
- Technology area (CPC Y)Emerging Cross-Sectional Technologies
- CPC primaryY10S435/876
- WIPO fieldBiotechnology
- WIPO sectorChemistry
Abstract
R- and S-1-Phenyl-1,3-propanediol, each of high optical purity, were prepared by a chemoenzymatic sequence starting with ethyl benzoylacetate. The first step was a catalytic hydrogenation of the .beta.-ketoester conducted at room temperature. The enzymatic hydrolysis of the resulting hydroxyester proceeded in a facile manner using a commercial preparation of the lipase from Pseudomonas fluorescens. The enzymatic hydrolysis proceeded at a moderate rate (350 mg lipase/0.10 mol of racemic ester required a 20-hour reaction time with an enantiomeric rate ratio (E value) of 36). The hydrolysis was run to 45-50% conversion to afford isolated S-3-phenyl-3-hydroxypropionic acid of 85-90% ee after separation from the residual ester (aqueous base extraction). The optical purity of the hydroxy acid was determined by conversion to the methyl ester (CH.sub.3 I, KHCO.sub.3, acetone), and derivatization with S-MTPA-Cl, and .sup.1 H NMR analysis. A single recrystallization of the isolated acid afforded optically pure (>98% ee) S-3-phenyl-3-hydroxypropionic acid in an overall 36% yield from the racemic ester. The acid was reduced with borane in THF to afford optically purs S-diol in 97% yield after …
Source: USPTO / EPO open patent data. Objective bibliographic and citation counts.