Hydrochloric Acid → Zantac

Participants

Reaction Steps

The seeding material of pure Form 1 ranitidine hydrochloride may be prepared by dissolving ranitidine in a solvent, preferably methylene chloride, at room temperature (20° to 25° C.), wherein the ratio of ranitidine to methylene chloride is from about 1:1 to 1:5, preferably 1:4, and treating the solution thus obtained with aqueous concentrated hydrochloric acid (e. g., 35 to 38% w/w). The hydrochloric acid and ranitidine may be mixed without cooling to form a reaction mixture. Preferably, however, the hydrochloric acid and ranitidine are mixed with cooling at -5° C. to 10° C. The reaction mixture is then heated under reflux and during heating, water is stripped off under azeotropic conditions. Preferably, the reaction mixture is heated under reflux for at least 4 hours, more preferably for approximately 6.5 hours. Alternatively, the reaction may be carried out under mild reaction conditions, such as, for example from 0° to 10° C. up to 20° to 25° C. for approximately 6.5 hours. The Form 1 ranitidine hydrochloride crystals that are formed are then filtered off from the crystallization medium, washed with ethanol and dried.

Provenance & Evidence