反应详情

Dissolve 1-(2-{4-[2-(2,5-difluoro-phenyl)-6-methoxy-naphthalen-1-ylmethyl]-phenoxy}-ethyl)-piperidine in 20 mL acetonitrile and chill in an ice bath. Add 1.5 mL of boron tribromide with swirling and allow to warm to room temperature. Pour this mixture into a two-phase mixture of saturated sodium bicarbonate solution and a 3/1 mixture of chloroform/isopropanol. Wash the organic layer with water and dry over 3 Å molecular sieves. Concentrate the organic layer and purify on a silica gel column, eluting with a 0-10% methanol/methylene chloride gradient. Evaporate the solvent and convert the compound to the salt with HCl to give 369 mg (82%) of the title compound: 1H-NMR (CDCl3, 300 MHz) δ7.77 (d, J=8.7 Hz, 1H); 7.61 (d, J=8.1 Hz, 1H); 7.28-7.25 (m, 1H); 7.11-6.94 (m, 4H); 6.89-6.83 (m, 1H); 6.74 (d, J=8.7 Hz, 2H); 6.57-6.54 (m, 2H); 4.31-4.10 (d, 2H); 4.04 (t, J=6.0 Hz, 2H); 2.80-2.80 (m, 2H); 2.59-2.59 (m, 4H); 1.68-1.65 (m, 4H); 1.48-1.46 (m, 2H).

1. temperaturechill in an ice bath
2. additionPour this mixture
3. washWash the organic layer with water
4. customdry over 3 Å molecular sieves
5. concentrationConcentrate the organic layer
6. custompurify on a silica gel column
7. washeluting with a 0-10% methanol/methylene chloride gradient
8. customEvaporate the solvent