Methanol → (4S)-5-cyclohex-1-en-1-yl-6-{(R)-hydroxy[4-(trifluoromethyl)phenyl]methyl}-7-isopropyl-2,2-di-methylchroman-4-ol

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Reaction Steps

230 μl (1.27 mmol) of borane/N,N-diethylaniline complex are added very slowly to a solution of 7.10 mg (50 μmol) of (1R,2S)-1-aminoindan-2-ol in 7.5 ml of tetrahydrofuran, and the mixture is stirred at room temperature for 30 min. A solution of 150 mg (320 μmol) of 5-cyclohex-1-en-1-yl-6-{hydroxy[4-(trifluoromethyl)phenyl]methyl}-7-isopropyl-2,2-dimethyl-2,3-dihydro-4H-chromen-4-one (Example 35A) in 7.5 ml of tetrahydrofuran are then added very slowly dropwise over a period of 30 min. The mixture is stirred 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 column chromatography on silica gel (mobile phase: gradient cyclohexane→cyclohexane/ethyl acetate 20:1→10:1→1:1) and subsequent preparative HPLC (method 1) gives the diastereomerically pure target compounds, which for their part are present as a mixture of two rotamers.

Provenance & Evidence