Methanol → [(4S)-5-(4-Fluorophenyl)-4-hydroxy-7-isopropyl-2,2-dimethyl-3,4-dihydro-2H-chromen-6-yl][4-(trifluoromethoxy)phenyl]methanone

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Reaction Conditions

Reaction Steps

97 μl (540 μmol) of borane/N,N-diethylaniline complex are added slowly to a solution of 3.04 mg (20 μmol) of (1R,2S)-1-aminoindan-2-ol in 2.5 ml of tetrahydrofuran. The mixture is then cooled to 0° C., and a solution of 68 mg (140 μmol) of 5-(4-fluorophenyl)-7-isopropyl-2,2-dimethyl-6-[4-(trifluoromethoxy)benzoyl]-2,3-dihydro-4H-chromen-4-one (Example 26A) in 4 ml of tetrahydrofuran is then slowly added dropwise. The mixture is allowed to thaw slowly and stirred at room temperature overnight. To bring the reaction to completion, the reaction mixture is again cooled to 0° C., and a further 97 μl (540 μmol) of borane/N,N-diethylaniline complex are added. The mixture is then thawed slowly to room temperature and stirred at this 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) and subsequent chiral HPLC (method 2) gives the target compound.

Provenance & Evidence