Patent ID: 8247549

Claim:
A method for preparing 4-(6-Amino-purin-9-yl)-2(S)-hydroxy-butyric acid methyl ester, comprising the steps of: (1) performing a ring-closing reaction by a nucleophilic substitution between L-malic acid and a protective agent, a carbonyl compound having a structure of R 1 COR 2 or a diol-carbonyl condensation compound thereof, to selectively afford an intermediate I whose 1-carboxyl and 2-hydroxy groups were both protected simultaneously, wherein R 1 and R 2 are each independently one substituent selected from the group consisting of H, methyl, ethyl, n-propyl, n-butyl, phenyl and p-methoxyphenyl; (2) reducing the intermediate I obtained from step (1) by a reducing agent selected from the group consisting of a borane agent and a metal hydride to afford an intermediate alcohol II, wherein the 4-carboxyl group of the intermediate I was selectively reduced to the corresponding hydroxyl group; (3) esterifying the intermediate alcohol II obtained from step (2) by an acyl chloride selected from the group consisting of p-toluenesulfochloride, mesyl chloride, trifluoroacetyl chloride, trichloroacetyl chloride and acetyl chloride in the presence of a base to afford an intermediate III, wherein X is one selected from the group consisting of mesyloxyl, p-toluenesulfonyloxyl, trifluoroacetyloxyl, trichloroacetyloxyl and acetyloxyl; or, halogenating the intermediate alcohol II by a halogenating agent selected from the group consisting of phosphorus tribromide, phosphorus pentabromide, carbon tetrabromide/triphenylphosphine and iodine/triphenylphosphine to afford an intermediate III, wherein X is Br or I; (4) in the presence of a base and a phase transfer catalyst, performing a nucleophilic substitution between the intermediate III obtained from step (3) and adenine in an appropriate solvent at a suitable temperature to afford an intermediate IV; (5) deprotecting and methyl-esterifying the intermediate IV obtained from step (4) simultaneously in a methanol system in the presence of an acid or a base to afford 4-(6-Amino-purin-9-yl)-2(S)-hydroxy-butyric acid methyl ester.