HCID 131736819, compound → HCID 102196131, compound

Participants

Reaction Steps

Resolution of racemates is done by semi-preparative chiral HPLC such as e.g. with a 250×20 mm, 5 μL, CHIRALPAK® IA column. 5.2 g (25.2 mmol) of (+/−)-exo-6-(6-fluoro-pyridine-3-yl)-8-aza-bicyclo-[3.2.1]octane-8-carboxylic acid benzyl ester (III) are dissolved in 42 ml of a mobile solvent (MeCN/0.1% diethylamine). The injection volume is 1 ml. Separation was done under isocratic conditions with a flow of 20 ml/min. Detection is performed by means of a UV detector at a wavelength of 280 nm. The retention time of the (+)-enantiomer (VI) is approx. 8-13 min, that of the (−)-enantiomer (V) approx. 19-38 min. Both enantiomers are separately collected, after chiral HPLC the mobile solvent is removed by means of the rotary evaporator. The enantiomeric purity is determined by analytic chiral HPLC by means of a 250×4.6 mm, 5 μL, CHIRALPAK® IA column. 1 mg of the respective enantiomer is dissolved in 1 ml of a mobile solvent (MeOH/0.1% TEA). The injection volume is 10 μL. Separation was done under isocratic conditions with a flow of 1 ml/min. Detection is done at 280 nm. The retention time of the (+)-enantiomer (VI) is 11.5 min, that of the (−)-enantiomer (V) 17.5 min. 2.24 g (10.86 mmol, 43%, >99% ee, [α]D20 (CHCl3, c=0.5)=−30.9°) of (−)-(1R,5S,6S)-6-(6-fluoro-pyridine-3-yl)-8-aza-bicyclo[3.2.1]octane (V) and 2.2 g (10.67 mmol, 42%, >99% ee, [α]D20 (CHCl3, c=0.5)=)+29.0° of (+)-(1S,5R,6R)-6-(6-fluoro-pyridine-3-yl)-8-aza-bicyclo[3.2.1]octane (VI), respectively, is isolated as a colorless solid.

Provenance & Evidence