The invention belongs to the
pharmaceutical manufacturing field, which relates to a novel process for the preparation of substituted phenylacetic acids derivatives, especially relates to the preparation of 2-(4-(2-oxocyclopentyl)phenyl)
propanoic acid. The process for the preparation of the precursor form of
loxoprofen which use 1,4-di-halobenzyl compounds or disubstituted
benzyl compounds as starting material, is through the
substitution reaction of
cyclopentanone groups or its precursor compounds.Wherein X is
halogen, L1 is a suitable
leaving group selected from
halogen, OH, OMs, OTs, OTf and the like; L2 is a suitable
leaving group selected from
halogen, CN, OH, —CH2OH, —CHO, CH3NO2, ester group, —NR4R5, OTf, OTs, OMs, —C═CR6, —C≡CR7 and the like, wherein R4, R5, R6, R7 are short chain
alkyl groups; Z is
cyclopentanone group and its precursor form selected fromand the like; R3 is short chain
alkyl groups. L3 is a suitable
leaving group selected from halogen, OH, OMs, OTs, OTf and the like, or organometallic groups. The invention also include the detailed procedure to convert the precursor compounds of
cyclopentanone group to cyclopentanone, followed by the transformation of the precursor compounds of
loxoprofen to
loxoprofen.