Dexibuprofen → Ibuprofen, (+-)-

Participants

Reaction Conditions

Reaction Steps

Heptane is removed as stream 18, FIG. 1, by distillation in an evaporator at atmospheric pressure from a mixture [stream 15, FIG. 1] containing S(+)-ibuprofen (0.1912 moles, 39.43 g), R(-)-ibuprofen (0.5136 moles, 105.95 g), and heptane (ca. 390 g). During the distillation, water [30 g, stream 17] is injected into the base of the evaporator to help strip out the last traces of heptane and to minimize formation of ibuprofen ethyl ester. The molten evaporation residue [stream 33], which consists essentially of ibuprofen with an S/R ratio of 27/73, is first racemized by being heated under nitrogen at 220° C. for four (4) hours and is then distilled at about 220° C., 10 mm HgA in an evaporator to provide a distillate [stream 19] of substantially pure racemized ibuprofen (0.6907 moles, 142.48 g, S/R ratio of 47:53) and an undistilled residue [stream 20, 2.91 g] for incineration as a waste stream. Racemized ibuprofen distillate [stream 19] is recycled to the first crop crystallization of crude S(+)-ibuprofen lysinate.

Provenance & Evidence