Racemisation of R-Bupivacaine: A Key Factor in the Integrated and Economic Process for the Production of Levobupivacaine

Two methods for the racemisation of nonracemic bupivacaine and 2‘,6‘-pipecoloxylidide, a key intermediate in the synthesis of bupivacaine, are described. One uses carboxylic acids at high temperature and the other uses water and a cosolvent. The product obtained from the carboxylic acid racemisation is of suitable quality to generate commercial levobupivacaine hydrochloride (Chirocaine) 1[S], a less cardiotoxic alternative to bupivacaine hydrochloride (Marcaine) 1[R,S].