Invention Publication

METHOD FOR PRODUCING CENTANAFADINE
Abstract:
The present invention addresses the problem of finding a method for reliably producing (1R,5S)-1-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane hydrochloride, wherein crystalline polymorphs can be controlled with industrially easy operations. Provided is a method for producing a crystalline form of (1R,5S)-1-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane hydrochloride, the method comprising: step (a) for heating and dissolving (1R,5S)-1-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane hydrochloride in a solvent including an alcohol-based solvent; step (b) for cooling the dissolved product of step (a) to a temperature, at which crystals of (1R,5S)-1-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane hydrochloride precipitate, to nucleate the crystals; step (c) for heating a mixture containing the crystals obtained by nucleation to a temperature at which only a specific crystalline form selectively remains; and step (d) for cooling the mixture heated in step (c) to obtain the crystalline form.
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