Patent ID: 8450487

Claim:
A process for the preparation of pharmaceutical grade cis-2-methylspiro(1,3-oxathiolane-5,3′)quinuclidine hydrochloride having a purity >99.5% comprising: a) treating an epoxide of 3-methylenequinuclidine with hydrogen sulfide gas in a solvent selected from the group consisting of methanol, isopropanol, butanol, and mixtures thereof to obtain 3-hydroxy-3-mercaptomethyl quinuclidine; b) treating 3-hydroxy-3-mercaptomethyl quinuclidine with acetaldehyde in the presence of a boron trifluoride etherate to generate 2-methylspiro(1,3-oxathiolane-5,3′)quinuclidine base; c) treating the 2-methylspiro(1,3-oxathiolane-5,3′)quinuclidine base with hydrochloric acid to form a racemic hydrochloride salt; d) isomerizing the racemic hydrochloride salt with a Lewis acid and an organic solvent to obtain the isomer cis-2-methylspiro(1,3-oxathiolane-5,3′)quinuclidine having a purity of >90%; e) Purifying the cis isomer having >90% purity by treatment with an inorganic acid and an organic solvent to obtain the cis isomer having a purity of >99.5%.