Methanol → (4s)-5-(4-Fluorophenyl)-6-{(r)-hydroxy[4-(trifluoromethoxy)phenyl]methyl}-7-isopropyl-2,2-di-methylchroman-4-ol

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Reaction Conditions

Reaction Steps

140 μl (800 μmol) of borane/N,N-diethylaniline complex are added slowly to a solution of 4.45 mg (30 μmol) of (1R,2S)-1-aminoindan-2-ol in 5 ml of tetrahydrofuran. The mixture is then cooled to 0° C., and a solution of 100 mg (200 μmol) of rac-5-(4-fluorophenyl)-6-{hydroxy[4-(trifluoromethoxy)phenyl]methyl}-7-isopropyl-2,2-dimethyl-2,3-dihydro-4H-chromen-4-one (Example 24A) in 5 ml of tetrahydrofuran is then slowly added dropwise. The mixture is allowed to thaw slowly and stirred at room temperature overnight. Methanol is then added, and the solvent is removed under reduced pressure. The residue is taken up in ethyl acetate and washed in each case twice with 1 M hydrochloric acid and saturated sodium bicarbonate solution and once with saturated sodium chloride solution. The organic phase is dried over sodium sulfate and then concentrated under reduced pressure. Purification of the residue by preparative HPLC (method 1) gives the diastereomerically pure target compounds.

Provenance & Evidence