Peracetic Acid → Naproxen

HRID 1599189Notes

Reaction equation

HRID 1599189 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH:9]=[C:8]([C@H:13]([CH3:16])[CH:14]=[O:15])[CH:7]=[CH:6]2.CC1C=CC=C(C)[N+]=1[O-:25].C(OO)(=O)C>C(OCCCC)(=O)C.C(OCC)(=O)C>[CH3:16][C@H:13]([C:14]([OH:25])=[O:15])[C:8]1[CH:7]=[CH:6][C:5]2[CH:4]=[C:3]([O:2][CH3:1])[CH:12]=[CH:11][C:10]=2[CH:9]=1

Participants

6

Reactant 3

HCID 6585Peracetic AcidHCID 140832,6-Dimethylpyridine N-oxideHCID 1183081032305-59-2

Product 1

HCID 156391NaproxenYield 98.4%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 31272Butyl AcetateSolvent2×

Procedure

To a stirred solution of 3.32 g (15.5 mmol) of (S)-2-(6-methoxy-2-naphthyl)propionaldehyde (98.8% pure by GC) in n-butyl acetate (15.5 mL) cooled in a wet-ice bath (ca. 2° C.) was added 1.91 g (15.5 mmol) of 2,6-dimethylpyridine N-oxide (2,6-lutidine N-oxide). To this solution was then added slowly dropwise 1.77 g (23.2 mmol) of a 20.4 weight percent solution of peracetic acid in ethyl acetate, at a rate slow enough such that the reaction temperature did not exceed 10° C. (ca. 30 min). After the initial exotherm, the temperature returned to 2° C., and the reaction was maintained at this temperature for an additional 2 hours. Conversion of aldehyde at this time was ca. 99%, as monitored by GC (DB-1 column). The reaction solution was transferred into a separatory funnel, was diluted with n-butyl acetate (70 mL), and was washed with a 5% aqueous solution of sodium thiosulfate (Na2S2 O3, 15 mL). The butyl acetate layer was further washed with water (50 mL), and the combined water washes were back-extracted with n-butyl acetate (30 mL). The combined butyl acetate layers were extracted with two portions of a 5% aqueous solution of sodium hydroxide (NaOH, 65 mL each). The combined NaOH solutions of sodium naproxenate were acidified to pH=1 with a 5% aqueous solution of hydrochloric acid, precipitating the naproxen acid. The mixture was cooled in a wet-ice bath, and then was vacuum filtered through a #1 Whatman filter. The filter cake was washed with cold water (50 mL) and the white solid thus obtained was dried in a vacuum oven 60 hours at 55° C. (25 mm Hg), giving 3.51 g (98.4%) of naproxen.

Workup

  1. customdid not exceed 10° C.
  2. custom(ca. 30 min)
  3. customreturned to 2° C.
  4. temperaturethe reaction was maintained at this temperature for an additional 2 hours
  5. customThe reaction solution was transferred into a separatory funnel
  6. washwas washed with a 5% aqueous solution of sodium thiosulfate (Na2S2 O3, 15 mL)
  7. washThe butyl acetate layer was further washed with water (50 mL)
  8. extractionthe combined water washes were back-extracted with n-butyl acetate (30 mL)
  9. extractionThe combined butyl acetate layers were extracted with two portions of a 5% aqueous solution of sodium hydroxide (NaOH, 65 mL each)
  10. customprecipitating the naproxen acid
  11. temperatureThe mixture was cooled in a wet-ice bath
  12. filtrationfiltered through a #1 Whatman
  13. filtrationfilter
  14. washThe filter cake was washed with cold water (50 mL)
  15. customthe white solid thus obtained
  16. customwas dried in a vacuum oven 60 hours at 55° C. (25 mm Hg)

Sources & evidence

ORD record
ord-37be9b6100594605b2a42a53c0b6af78
Source dataset
uspto-grants-1998_04
Patent number
US05739385

Reaction notes

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