Patent ID: 7569687

Claim:
A process for the preparation of the quaternary ammonium salt, Rocuronium bromide, of formula I comprising: (a) combining a starting Compound VI having about 10% to about 40% area by HPLC of Compound VI-a with a water miscible organic solvent to obtain a suspension; (b) stirring the suspension at a temperature of about 60° C. to about 80° C. to obtain a mixture; (c) adding water to the mixture; (d) isolating Compound VI from the mixture, wherein the isolated Compound VI has less than about 3% area by HPLC of Compound VI-a; (e) forming a solution of Compound VI having less than about 3% of compound VI-a, and a water miscible organic solvent optionally combined with a water immiscible organic solvent; (f) adding at least one reducing agent to the solution at a temperature of about −15° C. to about 10° C. to obtain a mixture; (g) stirring the mixture at a temperature of about 20° C. to about 24° C.; (h) isolating Compound IV from the mixture having a purity of at least 85% area by HPLC; (i) forming a suspension of Compound IV, morpholine, and at least one acid catalyst; (j) stirring the suspension at a temperature of about 100° C. to about reflux for about 24 hours to about 48 hours; (k) isolating Compound VII from the suspension; (l) combining Compound VII, a polar organic solvent, and at least one acetylating reagent with at least one base to obtain a mixture; (m) isolating Compound VIII from the mixture; (n) combining Compound VIII, a polar aprotic organic solvent, allyl bromide, and at least one inorganic base to obtain a mixture; (o) and isolating rocuronium bromide from the mixture.