SYNTHESIS OF NAPROXEN VIA REGIOSELECTIVE RING-OPENING OF (2S,3S)-EPOXY-1-BUTANOL

(S)-Naproxen was synthesized by the regioselective and stereospecific epoxide ring opening of (2S,3S)-epoxy-1-butanol (2) with diethyl-2-(6-methoxynaphthyl)aluminium (5) as the key step. Thus, treatment of diethylaluminate of 2 with 5 at 0-degrees afforded (2S,3S)-3-(6-methoxy-2-naphthyl)butan-1,2-diol (6), which was oxidized by sequential treatment with sodium periodate and potassium permanganate in a mixture of tert-butyl-alcohol and phosphate buffer (pH 7.0) to give naproxen in high enantiomeric purity.