合成路线1

1) Synthesis of intermediate (V): The reduction of 2,4,6-triisopropylbenzoyl chloride (I) with LiAlH4 in ethyl ether gives 2,4,6-triisopropylbenzyl alcohol (II) (1-4), which by reaction with SOCl2 in toluene is converted into 2,4,6-triisopropylbenzyl chloride (III). The reaction of (III) with NaCN or KCN in DMSO affords 2,4,6-triisopropylphenylacetonitrile (IV), which is hydrolyzed with aqueous H2SO4 or KOH in diethylene glycol/water, yielding the phenylacetic acid (V). 2) Synthesis of intermediate (III): The intermediate benzyl chloride (III) can also be obtained by direct chloromethylation of 1,3,5-triisopropylbenzene (XI) with paraformaldehyde/HCl in acetic acid. 3) Synthesis of intermediate (V): Phenylacetic acid (V) can also be obtained by condensation of 1,3,5-triisopropylbenzene (XI) with glyoxylic acid (XIV) by means of H2SO4 in refluxing acetic acid, yielding a mixture of acetoxyacetic acid (XV) and hydroxyacetic acid (XVI). This mixture is finally reduced with HI in acetic acid to the phenylacetic acid (V). 4) Synthesis of intermediate (IV): The acetonitrile (IV) can also be obtained by reaction of benzyl bromide (XII) with KCN in DMSO. 5) Synthesis of intermediate (XIII): Avasimibe can also be obtained by reaction of benzyl alcohol (II) with PBr3 in ether to give the benzyl bromide (XII), which is treated with Mg in THF to yield the corresponding Grignard reagent (XIII).