Asymmetrical synthesis of R-(+)-2-(4-Hydroxyphenoxy) propionic acid

Using optical L-lactic acid as the starting material,R-(+)-2-(4-hydroxyphenoxy)propionic acid was synthesized via esterification,sulfonylation and etherification reaction,and the configuration was reversed in etherification reaction.In sulfonylation reaction,using Et3N as a base and TEBAC as a catalyst,the molar ratio of L-ethyl lactate to p-toluenesulfonyl chloride to Et3N was 1∶1∶1.2,reaction temperature 0 ℃,reaction time 5 h,the yield of ethyl S-(-)-2-(4-toluenesulfonyloxy)lactate was 96.5% with the purity of 98.0%;In etherification reaction,using H2O as a solvent in N2 atmosphere,the molar ratio of hydroquinone to ethyl S-(-)-2-(4-toluenesulfonyloxy)lactate was 1.2∶1,reaction temperature 30 ℃,reaction time 6 h,under the optimum conditions,the yield of R-(+)-2-(4-hydroxyphenoxy)propionic acid was 72.4% based on L-lactic acid with the purity of 99.5%,and the optical purity was confirmed to be 97.9%.The structure of R-(+)-2-(4-hydroxyphenoxy)propionic acid was confirmed by 1H NMR,IR and MS.