Tetrahydrofuran → (4S)-5-(4-fluorophenyl)-6-{(R)-hydroxy[4-(trifluoromethoxy)phenyl]methyl}-7-isopropyl-3,4-di-hydrospiro[chromen-2,1'-cyclobutan]-4-ol

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Reaction Steps

Under argon, 1.5 mg (0.01 mmol) of (1R,2S)-1-aminoindan-2-ol are dissolved in 1.5 ml of abs. tetrahydrofuran, 69 μl (0.39 mmol) of borane/N,N-diethylaniline complex are added and the mixture is stirred at room temperature for 30 min. After this time, 50 mg (0.10 mmol) of 5-(4-fluorophenyl)-6-{hydroxy[4-(trifluoromethoxy)phenyl]methyl}-7-isopropylspiro[chromen-2,1′-cyclobutan]-4(3H)-one (Example 58A), dissolved in 2 ml of abs. tetrahydrofuran, are added at room temperature over a period of 10 min, and the mixture is then stirred at room temperature overnight. 2 ml of methanol are added, and the mixture is stirred for 15 min and then concentrated to dryness. The residue is taken up in ethyl acetate and washed twice with 1 N hydrochloric acid, twice with saturated sodium bicarbonate solution and twice with saturated sodium chloride solution. The organic phase is dried over sodium sulfate, filtered and concentrated. The crude product is purified by preparative thick-layer chromatography (mobile phase: cyclohexane/ethyl acetate 5:1). This gives 13.5 mg (27% of theory, 78% ee) of Example 38 and 16.5 mg (33% of theory) of Example 39.

Provenance & Evidence