合成路线1

The bromination of 2,7-dimethylnaphthalene (I) with N-bromosuccinimide (NBS) and UV light in CCl4 gives the monobromo derivative (II), which is treated with 2-nitropropane/NaOMe to yield 7-methylnaphthalene-2-carbaldehyde (III). The reaction of (III) with hydroxylamine-O-sulfonic acid affords the nitrile (IV), which is brominated with NBS as before to give 7-(bromomethyl)naphthalene-2-carbonitrile (V). The condensation of (V) with 2-[4-[1-(tert-butoxycarbonyl)pyrrolidin-3(S)-yloxy]phenyl]acetic acid ethyl ester (VI) by means of lithium bis(trimethylsilyl)amide yields 2-[4-[1-(tert-butoxycarbonyl)pyrrolidin-3(S)-yloxy]phenyl]-3-(7-cyano-2-naphthyl)propionic acid ethyl ester (VII) as a diastereomeric mixture. This mixture was worked up as already described to obtain the target compound DX-9065a.