合成路线1

Treatment of 2-(trityloxy)ethanol (I) with bromoacetic acid (II) and n-BuLi in THF affords ethoxyacetic acid derivative (III), which is then converted into ethyl ester (IV) by means of EtOH and DCC in CH2Cl2 in the presence of 4-pyrrolidinopyridine. Reaction of (IV) with Grignard reagent, prepared from 2-bromo-3-methylthiophene (V) and Mg turnings in THF, provides compound (VI), which is then converted into the corresponding tosylate derivative (VII) by treatment with BuLi and p-toluenesulfonyl chloride (p-TsCl) in toluene. Reaction of (VII) with (R)-ethyl nipecotate (VIII) and K2CO3 yields ethyl ester (IX), which is finally hydrolyzed with aqueous NaOH in EtOH followed by treatment with diluted HCl.