合成路线1

The synthesis of atorvastatin [14C]-labeled on the side chain has been described: The reaction of [14C]-labeled sodium acetate (I) with phthaloyl chloride (II) in refluxing xylene gives the acyl chloride (III), which is treated with 1,2,2-triphenyl-1(S),2-ethanediol (IV) in dichloromethane yielding the expected monoacetate (V). The condensation of (V) with the pyrrolepropionaldehyde (VI) by means of lithium diisopropylamide (LDA) in THF affords the chiral beta-hydroxyester (VII), which is transesterified with sodium methoxide in methanol providing the corresponding methyl ester (VIII). The condensation of (VIII) with tert-butyl acetate (IX) by means of LDA in THF gives the beta-oxo-delta-hydroxyester (X), which is regioselectively reduced to the dihydroxyester (XI) by means of BEt3, NaBH4 and H2O2 in THF. The hydrolysis of (XI) with NaOH in THF/water, followed by acidification yields the free acid (XII), which is heated in refluxing toluene in a Dean-Stark trap to provide lactone (XIII). The reaction of (XIII) with NaOH in THF/methanol gives the corresponding sodium salt (XIV), which is finally treated with CaCl2 in the same solvent.