反应详情

Convert [4-(2-azepan-1-yl-ethoxy)-phenyl]-[2-(2,6-difluoro-phenyl)-6-methoxy-naphthalen-1-yl]-methanone (2.5 g, 4.8 mmol) into the hydrochloride salt and charge a flask with the solid salt. Dissolve the material in 200 mL methylene chloride and chill in ice. Add to this mixture boron tribromide (5.0 mL, 53.0 mmol) while swirling. Stir the reaction at room temperature for one hour and pour into a two phase system of saturated sodium bicarbonate and an organic layer consisting of a 3/1 mixture of chloroform/isopropanol. Shake to extract the product, separate the organic layer, dry over 3 Å molecular sieves and evaporate the solvent under vacuum. Purify on a silica gel column eluting with a 0-10% methanol/methylene chloride gradient to give 1.3 g (54%) of the title compound: 1H-NMR (CDCl3, 400 MHz) δ 7.79-7.74 (d, 1H); 7.58 (d, J=8.4 Hz, 2H); 7.50 (d, J=8.8 Hz, 1H); 7.33-7.30 (d, 1H); 7.17 (d, J=2.4 Hz, 1H); 7.16-7.08 (m, 1H); 6.99-6.95 (dd, 1H); 6.77-6.73 (m, 2H); 6.68 (d, J=9.2 Hz, 2H); 4.11 (t, J=6.0 Hz, 2H); 3.05-2.99 (t, 2H); 2.90-2.84 (m, 4H); 1.71-1.71 (m, 4H); 1.63-1.60 (m, 4H).

1. temperaturechill in ice
2. customthe reaction at room temperature for one hour
3. extractionShake to extract the product
4. customseparate the organic layer
5. customdry over 3 Å molecular sieves
6. customevaporate the solvent under vacuum
7. customPurify on a silica gel column
8. washeluting with a 0-10% methanol/methylene chloride gradient