Acetic Acid → Naproxen

Temperature

2 °C

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.

1. customdid not exceed 10° C
2. temperatureheated to 50° C.
3. temperatureThe solution was cooled in a wet-ice bath
4. customprecipitation
5. filtrationfiltered through a #2 Whatman
6. filtrationfilter
7. customThe light purple solid thus obtained
8. washwas washed with 20 mL water
9. customwas dried in a vacuum oven 14 hours at 55° C. (25 mm Hg)

ORD record

ord-f1bbe85c9c15410faeb81cafe44180a1

Source dataset

uspto-grants-1998_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05739385