Acetic Acid → Naproxen

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of 1.0 g (4.67 mmol) of (S)-2-(6-methoxy-2-naphthyl)propionaldehyde in absolute ethanol (5.0 mL) cooled in a wet-ice bath (ca. 2° C.) was added 0.27 mL (0.28 g, 4.67 mmol) of glacial acetic acid followed by 0.62 mL (0.70 g, 4.67 mmol) of triethanolamine. To this solution was then added slowly dropwise 2.25 mL (7.0 mmol) of a 23.0 weight percent solution of peracetic acid in ethyl acetate, at a rate slow enough such that the reaction temperature did not exceed 10° C. The reaction mixture was stirred at 2° C. for 2 hours, then an additional 2.25 mL (7.0 mmol) of the peracetic acid solution was added to complete the conversion of the aldehyde (4 hours total). The solution was transferred into a larger flask with the aid of ethanol (5 mL), heated to 50° C., and was diluted with water (40 mL). The solution was cooled in a wet-ice bath causing precipitation, and was vacuum filtered through a #2 Whatman filter. The light purple solid thus obtained was washed with 20 mL water and was dried in a vacuum oven 14 hours at 55° C. (25 mm Hg), giving 0.79 g (73.5%) of naproxen. Chiral phase HPLC analysis indicated a ratio of S:R naproxen of 95.8: 4.2, the same as that obtained by an independent oxidation method.

Provenance & Evidence