Racemic cis-6-chloro-3-phenylindan-1-ol → (1S,3S)-6-chloro-3-phenylindan-1-ol

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Reaction Steps

Racemic cis-6-chloro-3-phenylindan-1-ol (V) (prepared as described in PCT/DK04/000546, i.e. adapting the method described in Bøgesø et al. J. Med. Chem. 1995, 38, 4380-4392 using ethanol as solvent, and performing the reaction at approximately 0° C.) (492 grams) is resolved by preparative chromatography, using a CHIRALPAK® AD column, 10 cm ID X 50 cm L, 10 μm at 40° C. Methanol is used as mobile phase at a flow rate of 190 ml/min, detection is performed using a UV detector at 287 nm. The racemic alcohol (V) is injected as a 50,000 ppm solution in methanol; 90 ml is injected with intervals of 28 min. All the fractions, which contain the title compound with more than 98% enantiomeric excess, are combined and evaporated to dryness using a rotary evaporator, followed by drying in vacuo at 40° C. Yield 220 grams as a solid. Elemental analysis and NMR conform to the structure, the enantiomeric excess is higher than 98% according to chiral HPLC, [α]D20+44.50 (c=1.0, methanol).

Provenance & Evidence