Asymmetric Catalytic Hydrogenation Synthesis Ethyl(S)-3-hydroxybutyrate

Ethyl(S)-3-hydroxybutyrate(EHB)is anvery important chiralalcohol.Homochiral ethyl 3-hydroxybutyrate is a very important chiral building block and plays a key role in starting material for synthesis of chiral natural products and pharmaceutical preparations:(R)-EHB can be used for synthesis of ?-lactamase inhibitor,thienamycin,(+)-decarestrictine L,etc.While,(S)-EHB is an important raw material for the synthesis of insect pheromone,citronellol and carbapenem antibiotics.The analytical mehtod by chiral GC was set up to chase the experiment and high performance liquid chromatographic(HPLC)method was establishedfor the enantiomeric separation of ethyl 3-hydroxybutyrateon chiralcel OD-H column.The influences of the mobile phase composition and flow rate on enantioseparation of ethyl 3-hydroxybutyrate were studied.The optimized chromatographic conditions were hexane-isopropanol(100:5,v/v)as mobile phase with a flow rate of 1 mL-min-1 and detection at the wave length of 215 nm.Self-made Ruthenium-based organometal compound[RuCl2(COD)]2 was used as the catalyst,(S)-BINAP as chiral ligands.In the presence of additives,(S)-EHB was synthetized by asymmetric hydrogenation method.Single factor experiment and orthogonal experiment were carried out to obtain optimal reaction conditions.The results showed that,when the process was taken on 100 g-L-1(EtOH)ethyl acetoacetate as the basis with 24 mg-L-1(EtOH)normal concentration of catalyst and160 mL-L-1(EtOH)normal concentration of addition agent at 100?,0.5 MPa,for 6.4 h,ethyl acetoacetate can be converted completely and enantiomer excess value can reach more than 98%.The products were separated and purified by silica gel column chromatography.The volume ratio of the petroleum ether and ethyl acetate was primarily investigated.Results indicated that with the volume ratio of 8:1,it gave the best separating effect.The purified product ethyl(S)-3-hydroxybutyrate was determined by IR,1H-NRM,13C-NRM.The structure and configuration were accordant to the target compound.