| 摘要 |
<p>Disclosed is a process for the preparation of a quaternary derivative of a tertiary N-substituted morphinan alkaloid having a protected C(3) hydroxy substituent of formula 111a, the process comprising (i) combining a C(3)-O-protected tertiary N-substituted morphinan alkaloid substrate of formula 111 with an alkylating agent in an anhydrous solvent system comprising at least 25 wt% of an anhydrous aprotic dipolar solvent, to form a reaction product mixture containing the quaternary derivative of the C(3)-O-protected tertiary N-substituted morphinan alkaloid substrate and any unreacted tertiary N-substituted morphinan alkaloid substrate, and (ii) adding a non-solubilizing solvent to the reaction product mixture to precipitate the quaternary derivative, the quaternary derivative having less solubility in the non-solubilizing solvent than in the dipolar aprotic solvent. (62) Divided Out of 579469</p> |
