Synthesis of naproxen via regioselective ring opening of (2 S ,3 S )‐epoxy‐1‐butanol

(S)‐Naproxen was synthesized by the regioselective and stereospecific epoxide ring opening of (2 S ,3 S )‐epoxy‐1‐butanol (2) with diethyl‐2‐(6‐methoxynaphthyl)aluminium (5) as the key step. Thus, treatment of di‐ethylaluminate of 2 with 5 at 0° afforded (2 S ,3 S )‐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 ( p H 7.0) to give naproxen in high enantiomeric purity.