Patent ID: 8101756
Filing Date: 2012-01-24
Classification: C07D

Abstract:
1. A process for the preparation of a quaternary N-alkyl morphin or morphinan alkaloid derivative of general formula (I) a or b: wherein A is —C(O)—, —C(S)—, —C(═CH A R R X Y is hydrogen, hydroxy, alkoxy, acyloxy, —O-tetrahydropyranyl (—OTHP), —OSiR starting from the tertiary N-alkyl morphin or morphinan alkaloid of general formula (II) a or (II) b wherein Z is hydroxy, alkoxy, acyloxy, —OTHP, —OSiR comprising the steps of: a) adding an alkylating agent to the compound of formula (II) a or b in presence of an aprotic, dipolar solvent to obtain a reaction mixture; b) adding a nucleophilic nitrogen, phosphorus or sulfur containing base to the reaction mixture to obtain the intermediate zwitterion of formula (III) a or b in suspended or dissolved form; c) adding a solvent comprising alcohol and/or water to the product mixture thereby precipitating the compound of formula (III) a or b; d) separating the precipitated compound of formula (III) a or b from the remaining mixture; and e) suspending the intermediate zwitterion (III) a or b in water and adding a compound of formula HX to produce the product of formula (I) a or b.