合成路线1

The reaction of adipic acid monomethyl ester (XIII) with SOCl2 gives the acyl chloride (XIV), which is brominated with NBS in carbon tetrachloride to yield 5-bromo-5-(chloroformyl)pentanoic acid methyl ester (XV). The reaction of (XV) with phenol (XVI) by means of DIEA in ethyl ether affords the mixed diester (XVII), which is reduced with tri-tert-butoxylithiumaluminum hydride in THF to provide 5-bromo-5-formylpentanoic acid methyl ester (XVIII). The cyclization of (XVIII) with chiral ethanone (XIX) by means of DIEA in hot dioxane gives the methyl ester (XX) of the target compound, which is finally hydrolyzed with NaOH in ethanol/water to obtain the target acid . The intermediate chiral ethanone (XIX) has been obtained as follows: The reaction of the chiral alcohol (VIII) with 4-hydroxybenzoic acid methyl ester (XXI) under Mitsunobu conditions (DEAD, PPh3) gives the chiral ether (XXII), which is then condensed with 2-methylpyridine (XXIII) by means of LiHMDS in THF to yield the target ethanone.