Preparative method of R-(-)-lbuprofen by diastereomer crystallization.

The economic and effective method for preparation of R-(-)-ibuprofen by diastereomer crystallization was developed. R-(-)-ibuprofen was resolved from racemic ibuprofen by forming R-(-)-ibuprofen-R-(+)-alpha-methylbenzylamine diastereomeric salt with R-(+)-alpha(-methylbenzylamine and crystallization. The purity of R-(-)-ibuprofen-R-(+)-alpha-methylbenzylamine diastereomeric salt was tested and confirmed using HPLC and 1H-NMR method. The pure diastereomeric salt collected from repeated recrystallization was further fractionated by liquid-liquid extraction to the pure enantiomer without racemization. R-(-)-ibuprofen was recovered producing overall yield of 2.4% with the purity more than 99.97%.