反应详情

Tert-butyl({6-chloro-4-[4-chloro-2-(2,6-difluorobenzoyl)phenyl]pyridin-3-yl}-methyl)carbamate (165.0 mg, 0.3345 mmol) was dissolved in methylene chloride (5 mL). Trifluoroacetic acid (5 mL, 0.06 mol) was added and the reaction was stirred at room temperature under an atmosphere of nitrogen overnight. Water (20 mL) and methylene chloride (15 mL) were added and the resulting mixture was stirred while solid sodium carbonate (4.50 g, 0.04 mol) was slowly added with stirring. The resulting basic mixture was stirred at room temperature for 30 minutes and then transferred to a separatory funnel. The organic layer was separated and the aqueous phase was extracted with additional methylene chloride (10 mL). The organic extracts were combined, washed with water (10 mL) and brine (10 mL). The organic phase was dried over sodium sulfate, filtered and concentrated in vacuo. The resulting white solid was purified by column chromatography on silica gel (elution gradient from dichloromethane to 7.5% ethyl acetate/dichloromethane) to yield 2,9-dichloro-7-(2,6-difluorophenyl)-5H-pyrido[3,4-d][2]-benzazepine (108 mg, 86%) as a white solid. The product structure was confirmed by NMR and MS.

1. additionwas slowly added
2. stirringwith stirring
3. stirringThe resulting basic mixture was stirred at room temperature for 30 minutes
4. customtransferred to a separatory funnel
5. customThe organic layer was separated
6. extractionthe aqueous phase was extracted with additional methylene chloride (10 mL)
7. washwashed with water (10 mL) and brine (10 mL)
8. dry with materialThe organic phase was dried over sodium sulfate
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. customThe resulting white solid was purified by column chromatography on silica gel (elution gradient from dichloromethane to 7.5% ethyl acetate/dichloromethane)