反应详情

To a round bottom flask add (5-fluoro-2-{6-hydroxy-1-[4-(2-piperidin-1-yl-ethoxy)-benzoyl]-naphthalen-2-yl}-phenyl)-carbamic acid tert-butyl ester (0.060 g, 0.103 mmol), dichloromethane (1.25 mL), anisole (0.15 mL, 1.39 mmol) and trifluoroacetic acid (0.25 mL). Stir the reaction for 1.5 hour at ambient temperature. Add trifluoroacetic acid (2.0 mL) and sodium borohydride (0.024 g, 0.62 mmol) and stir the reaction at ambient temperature for 1.5 hours. Add more sodium borohydride (0.024 g, 0.62 mmol) and stir the reaction at ambient temperature an additional 2 hours. After aqueous work-up and purification LC/MS showed significant amounts of the (M-2) intermediate, so take this material up in acetic acid (3.0 mL) and to it add sodium cyanoborohydride (0.032 g, 0.51 mmol). Stir this mixture for 1.5 hours at ambient temperature. Add more sodium cyanoborohydride (0.032 g, 0.51 mmol) and stir an additional 1.5 hours at ambient temperature. Quench the reaction with saturated aqueous sodium bicarbonate. Extract the resulting aqueous mixture into ethyl acetate. Wash the combined extracts with saturated aqueous sodium bicarbonate, H2O and brine; then dry (sodium sulfate) and evaporate the filtrate in vacuo. Purify the resulting residue by radial chromatography over silica (5%-10% methanol gradient in dichloromethane) to provide 17 mg (35%) of the title compound: mass spectrum (ion spray) m/z=469 (M+H).

1. customthe reaction for 1.5 hour at ambient temperature
2. customthe reaction at ambient temperature for 1.5 hours
3. stirringstir
4. customthe reaction at ambient temperature an additional 2 hours
5. customAfter aqueous work-up and purification LC/MS
6. stirringStir this mixture for 1.5 hours at ambient temperature
7. stirringstir an additional 1.5 hours at ambient temperature
8. customQuench
9. customthe reaction with saturated aqueous sodium bicarbonate
10. extractionExtract the resulting aqueous mixture into ethyl acetate
11. washWash the combined extracts with saturated aqueous sodium bicarbonate, H2O and brine
12. dry with materialthen dry (sodium sulfate)
13. customevaporate the filtrate in vacuo
14. customPurify the resulting residue by radial chromatography over silica (5%-10% methanol gradient in dichloromethane)