Development of Highly Efficient Resolutions of Racemic Tramadol Using Mandelic Acid

Two methods for the resolution of tramadol are described. One uses the active pharmaceutical ingredient (API), tramadol hydrochloride as input material. The other utilises the crude free base obtained from the Grignard reaction on tramadol Mannich base. Both resolutions use mandelic acid; the cost and process implications of each approach are discussed.