Synthesis of 3‐ O ‐Carboxyalkyl Morphine Derivatives and Characterization of Their Acid‐Base Properties

The C-3 phenolic hydroxy group containing morphine derivatives (morphine, oxymorphone, naloxone, naltrexone) are excellent candidates for the synthesis of 3-O-functionalized molecules. Achieving free carboxylic gives opportunity further modification and conjugation that could be used immunization immunoassays. For this purpose ethyl bromo- chloroacetate can as O-alkylating agents. Hydrolyzing products affords appropriate 3-O-carboxyalkyl derivatives. As these molecules contain an acidic a basic functional protonation macro- microconstants were determined too, using pH-potentiometry NMR-pH titration, beside fully characterizing their structure IR, CD, NMR HR-MS measurements.