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

HRID 2096309Notes

Reaction equation

HRID 2096309 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C@@H:6]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[CH2:7][C@H:8]2[OH:11])=[CH:4][CH:3]=1>C(O)C.CO>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C@H:6]([C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=3)[CH2:7][C@@H:8]2[OH:11])=[CH:4][CH:3]=1

Participants

4

Reactant 1

HCID 59245334Racemic cis-6-chloro-3-phenylindan-1-ol2×

Product 1

HCID 11521607(1S,3S)-6-chloro-3-phenylindan-1-ol

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 887MethanolSolvent2×

Procedure

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×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 +44.5° (c=1.0, methanol).

Workup

  1. customthe reaction at approximately 0° C.) (492 grams)
  2. customat 40° C
  3. customis injected with intervals of 28 min

Sources & evidence

ORD record
ord-1b0d4a1899cd42a88fccd0e5a6f5923e
Source dataset
uspto-grants-2013_05
Patent number
US08450324B2

Reaction notes

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