Synthesis of Ethyl(S)-2-Ethoxy-3-(4-hydroxyphenyl)propionate

Ethyl(S)-2-ethoxy-3-(4-hydroxyphenyl)propionate(1) was prepared via a racemic synthetic route.Ethyl 2-chloride-2-ethoxyacetate(3) was synthesized from ethyl 2,2-diethoxyacetate(2) in a yield of 93%,which reacted with triethyl phosphate to give triethyl phosphonocetate(4) in a yield of 95%.Compound 4 was condensed with 4-benzyloxybenzaldehyd by Horner Wadswordth Emmons reaction to produce ethyl(Z,E)-2-ethoxy-3-(4-benzyloxy phenyl)propenonate(5) in a yield of 94%,which was hydrogenated to give ethyl(R,S)-2-ethoxy-3-(4-hydroxyphenyl) propionate(6) in a yield of 98%.The corresponding carboxylic acid(7) was obtained by the hydrolysis of compound 6 under basic conditions in a yield of 96%.Chemical resolution of compound 7 with chiral amine R-(α)-methyl benzamethanamine produced compound 8.The(esterification) of compound 8 produced product 1,and its yield and ee value were 95% and 98.3%,respectively.