合成路线1

The key diaryl ethyl fragment of LY293111 begins with the deprotonation and alkylation of 1,3-dimethoxybenzene (VII) to provide compound (VIII). Two routes may be used to construct the diaryl ether phenol (X). The first route, utilizing an Ullmann ether synthesis, begins with the demethylation of (VIII) with molten pyridinium hydrochloride to give diol (IX). Subsequent coupling of (IX) with methyl 2-iodobenzoate in the presence of copper and potassium carbonate in refluxing pyridine provides the target phenol (X). In the alternative route, compound (VIII) is mono-demethylated with sodium ethanethiolate in hot N,N-dimethylformamide to provide phenol (XI). The addition of 2-fluorobenzonitrile to (XI), mediated by potassium fluoride-alumina and 18-crown-6 in refluxing acetonitrile, provides nitrile (XII). Boron tribromide-assisted demethylation of (XII), followed by hydrolysis and esterification, completes the alternate synthesis of intermediate (X).