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° 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° 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.
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