The optical resolution of 2,5-diamino-2-(difluoromethyl)pentanoic acid is performed as follows: The cyclization of its corresponding methyl ester (I) by means of sodium methoxide in methanol gives the racemic piperidone (II), which is submitted to optical resolution with (-)-binaphthylphosphoric acid yielding after crystallization and acidification with HCl the (+) and (-) piperidones (III) and (IV). Finally, both compounds are treated with refluxing 6N HCl to afford the target enantiomers.
By reaction of N2,N5-dibenzylidinolysine methly ester (I), with chlorodifluoromethane (II) in the presence of lithium diisopropylamide, followed by acid hydrolysis of the ester. Isolated as the monohydrochloride salt, monohydrate.