反应详情

Dissolve 1-{2-[4-(8-fluoro-2-methoxy-5H-6-thia-chrysen-5-yl)-phenoxy]-ethyl}-piperidine (330 mg, 0.67 mmol) in methylene chloride (6.0 mL) and add 2M HCl in ether (0.67 mL). Concentrate in vacuo and dissolve in dry methylene chloride (6.0 mL). Add 2-methyl-2-butene (0.71 mL, 6.7 mmol) and cool to 0° C. under nitrogen. Add boron tribromide (0.25 mL, 2.7 mmol) slowly and stir at 0° C. for 20 minutes. Pour the reaction into saturated aqueous sodium bicarbonate and extract with methylene chloride/methanol (4:1). Dry organic layer with sodium sulfate, filter and concentrate in vacuo. Purify the resultant oil over silica gel (0% to 3% methanol in methylene chloride). Dissolve the resultant oil in methylene chloride (3 mL) and add 2M HCl in ether (0.5 mL). Remove the solvent in vacuo and place in a 50° C. vacuum oven overnight to yield 225 mg (65%) of the title compound: mass spectrum (ion spray) m/z=486.3 (M−Cl).

1. concentrationConcentrate in vacuo
2. dissolutiondissolve in dry methylene chloride (6.0 mL)
3. additionPour
4. extractionextract with methylene chloride/methanol (4:1)
5. filtrationDry organic layer with sodium sulfate, filter
6. concentrationconcentrate in vacuo
7. customPurify the resultant oil over silica gel (0% to 3% methanol in methylene chloride)
8. dissolutionDissolve the resultant oil in methylene chloride (3 mL)
9. additionadd 2M HCl in ether (0.5 mL)
10. customRemove the solvent in vacuo and place in a 50° C. vacuum oven overnight