PREPARATION OF CODEINE FROM MORPHINE

摘要

An improved process for the preparation of codeine from morphine comprises the steps of: a) reacting morphine with a methylating agent in the presence of a hydrocarbon solvent at a temperature of 100 to 215 DEG C under reflux conditions such that approximately 50 % or more of the hydrocarbon solvent is returned to the reaction mixture to substantially avoid the formation of codeine methyl ether; and b) recovering codeine from the reaction mixture. The process may include step a) above followed by b) cooling the reaction mixture to approximately 85 DEG C and adding water to terminate the reaction; c) raising the pH of the reaction mixture to approximately 11; d) separating the hydrocarbon solvent phase containing codeine and dimethylaniline; and e) adding a dilute mineral or organic acid and approximately 6 to 7 times the volume of water for each volume of hydrocarbon solvent to separate dimethylaniline and codeine.