Sodium Hydroxide → Ibuprofen, Sodium Salt

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55.41 g. portion of the crude enol-acetate solution from part A, representing 49.3 mmoles of 2-acetoxy-3-(4'-isobutylphenyl)-3-methylacrylonitrile (V) was placed in a 250 ml. one-necked flask and stirred magnetically while 10 ml. of water and 16.0 g. (200 meq.) of 50 percent sodium hydroxide solution were added. The mixture was stirred at 70° C. for 7 hours and cooled to 25° C. to effect hydrolysis of the enol-acetate and to form the sodium salt (VI). The ph of the mixture was adjusted to 11 with 12 percent sulfuric acid (3.5 ml.). Sodium hypochlorite solution (15 percent W/V, 30 meq.; 24.8 ml.) was added over 30 minutes with ice water cooling of the flask. Methylene chloride (10 ml.) and 0.8g. of a filter aid (Celite) were added and the mixture was slowly cooled to 0° C. After 3 hours the solids were filtered (3 minutes on a coarse frit) and washed with cold brine (8 ml. of saturated sodium chloride solution plus 3 ml. of ice) and with 10 ml. of cold methylene chloride. The cake was dried to give 9.68 g. A 1 gram sample was removed for cyanide assay; it showed 40 parts per million sodium cyanide. The remaining salt, 8.68 g. was slurried with water. The slurry gave a negative picric paper test, and then 56 ml. of Skellysolve B (SSB) and 8 ml. of 12 N sulfuric acid were added, with warming to 40° C. The mixture was filtered and phases were separated. The upper phase was washed with 20 ml. of warm water. The combined aqueous phase were back washed in sequence with a 20 ml. portion of SSB. The two SSB phases were then stirred with a mixture of sodium sulfate and decolorizing charcoal (0.5 g.), filtered through a filter aid and concentrated to about 15 ml. volume. The resulting acid solution was seeded with crystals of 2-(4'-isobutylphenyl)propionic acid and held at 0° C. for 2 hours. The resulting precipitate of 2-(4'-isobutylphenyl)propionic acid (1) was filtered, washed with two 3 ml. portions of cold SSB and dried overnight at 50° C. The yield of 2-(4'-isobutylphenyl)propionic acid, based upon the glycidonitrile starting material, with correction for removed analysis samples of the sodium salt was 8.00 g. (78.8 percent). A thin layer chromatogram analysis showed no impurity. The mother liquor still contained 0.120 g. of the acid (I).

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