Patent ID: 7569598

Claim:
A process for the isolation a) of the 3R,2′R stereoisomer of glycopyrronium bromide or iodide (formula II: A=Br or I), or b) of the 3S,2′S stereoisomer (formula IV: A=Br or I), or c) of the 3R,2′S stereoisomer of the thienyl analog of glycopyrronium (formula VI: A=Br or I), or d) of the 3S,2′R stereoisomer (formula VIII: A=Br or I), where a) for the isolation of the 3R,2′R stereoisomer of glycopyrronium bromide or iodide (formula II: A=Br or I), the diastereomer mixture consisting essentially of the 3R,2′R isomer and 3R,2′S isomer (formula III) or the diastereomer mixture consisting essentially of the 3R,2′R isomer and 3S,2′R isomer (formula IIIb) or b) for the isolation of the 3S,2′S isomer (formula IV: A=Br or I), the diastereomer mixture consisting essentially of the 3S,2′R isomer and 3S,2′S isomer (formula V) or the diastereomer mixture consisting essentially of the 3R,2′S isomer and 3S,2′S isomer (formula Vb) or c) for the isolation of the 3R,2′S stereoisomer of the thienyl analog of glycopyrronium (formula VI: A=Br or I), the diastereomer mixture consisting essentially of the 3R,2′S isomer and 3R,2′R isomer (formula VII) or the diastereomer mixture consisting essentially of the 3R,2′S isomer and 3S,2′S isomer (formula VIIb) or d) for the isolation of the 3S,2′R isomer (formula VIII: A=Br or I), the diastereomer mixture consisting essentially of the 3S,2′S isomer and 3S,2′R isomer (formula IX) or the diastereomer mixture consisting essentially of the 3S,2′R isomer and 3R,2′R isomer (formula IXb) is combined for re-crystallizing and the stereoisomer to be isolated in each case is precipitated and obtained in enriched form, wherein for the preparation of those tertiary, basic diastereomer mixtures employed in the quaternization which lead to the abovementioned quaternary diastereomer mixtures a solvent is selected from the group consisting of branched and unbranched alcohols having one to four carbon atoms, acetone, butanone and acetonitrile in which the diastereomer mixture dissolves readily in said solvent, and said solvent consisting of branched and unbranched alcohols having one to four carbon atoms is preferably methanol, ethanol, or combinations thereof, and the stereoisomer to be isolated in each case is precipitated to be obtained in enriched form, using a second solvent preferably selected from ethyl acetate and/or tert-butyl methyl ether causing crystallization.