合成路线1

In an alternative procedure, (2,2,2-trifluoroethoxy)acetic acid (VIII) was converted into acid chloride (IX) by means of oxalyl chloride, and then coupled with (S)-4-benzyloxazolidine-2-one (V) in the presence of butyllithium to afford the chiral imide (X). The boron enolate obtained by treatment of (X) with di-n-butylboron triflate and triethylamine was then condensed with aldehyde (XI) to produce, after oxidative work-up with H2O2, a mixture of 3 diastereomeric aldol products (XII). The major [3(2S,3R),4S] isomer was isolated by column chromatography, and subsequently reduced with triethylsilane and trifluoroacetic acid to the (S,S) dehydroxylated compound (XIII). Basic hydrolysis of the imide (XIII) as above furnished the title carboxylic acid. Alternatively, treatment of the imide (XIII) with methanolic NaOMe produced the methyl ester (XIV), which was finally hydrolyzed to the target carboxylic acid employing HCl in aqueous dioxan.