Borane → (4S)-6-(4-tert-Butylbenzyl)-5-(4-fluorophenyl)-7-isopropyl-3,4-dihydrospiro[chromen-2,1'-cyclo-butan]-4-ol

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Reaction Steps

Under argon, 1.4 mg (0.009 mmol) of (1R,2S)-1-aminoindan-2-ol are dissolved in 2 ml of abs. tetrahydrofuran, 66 μl (0.37 mmol) of borane/,N-diethylaniline complex are added and the mixture is stirred at room temperature for 30 min. After this time, 45 mg (0.092 mmol) of 6-[(4-tert-butylphenyl)(fluoro)methyl]-5-(4-fluorophenyl)-7-isopropylspiro[chromen-2,1′-cyclobutan]-4(3H)-one (Example 55A), 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 for 15 h. 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 thick-layer chromatography (mobile phase: cyclohexane/ethyl acetate 10:1). This gives 33.5 mg (77% of theory, 80% ee) of the title compound. Chromatographic separation of 60 mg of Example 36 on a chiral phase [column: Chiralpak AD-H, 250×20 mm; mobile phase: isopropanol/isohexane 3:97; flow rate: 15 ml/min; 24° C.; detection: 260 nm] gives 45 mg of the title compound having an ee of >99%.

Provenance & Evidence