Patent ID: 7285665
Filing Date: 2007-10-23
Classification: C07D

Abstract:
1. A process for the preparation of a quaternary derivative of a tertiary N-substituted morphinan alkaloid, the process comprising contacting a tertiary N-substituted morphinan alkaloid substrate with an alkylating agent in an anhydrous solvent system, wherein the solvent system comprises an aprotic dipolar solvent selected from the group consisting of dimethylacetamide, dimethylformamide, 1-methyl-2-pyrrolidinone, hexamethylphosphoramide, and mixtures thereof with the aprotic dipolar solvent constituting at least 25 wt % of the solvent system, the contacting is carried out within a temperature range of about 55° C. to about 85° C., the tertiary N-substituted morphinan alkaloid substrate and the quaternary derivative correspond to Formulae 1 and Formula 1A, respectively: A is —C(O)—, —C(S)—, —C(═CH A each R is independently hydrocarbyl, R R X Y, if present, is hydrogen, hydroxy, alkoxy, acyloxy, —OTHP, —OSiR Z is hydroxy, alkoxy, acyloxy, —OTHP, —OSiR the dashed lines between the carbon atoms at positions 6 and 7, 7 and 8, and 8 and 14, respectively, represent (i) carbon-carbon single bonds, (ii) carbon-carbon single bonds between positions 6 and 7 and between positions 8 and 14, and a double bond between positions 7 and 8, or (iii) conjugated carbon-carbon double bonds between positions 6 and 7 and positions 8 and 14, with the proviso that Y is not present if there is a double bond between the carbons at positions 8 and 14.