反应详情

温度

65 °C

To a solution of tert-butyl (trans-4-(((R)-3-fluoropyrrolidin-1-yl)methyl)cyclohexyl)carbamate (265 mg, 0.88 mmol) in THF (6 mL) was added aqueous 6N HCl (6 mL) and water (6 mL) and the reaction mixture was heated at 65° C. for 3 h. The reaction mixture was cooled to room temperature, diluted with satd. aq. sodium bicarbonate (50 mL) and 1 M aqueous sodium hydroxide (50 mL) and extracted with a mixture of CHCl3/isopropanol (3:1). The combined organic layers were dried over anhydrous sodium sulfate and concentrated to afford a white semisolid. The residue was dissolved in dioxane followed by the addition of (6-bromo-4-chloroquinolin-3-yl)(cyclopropyl)methanone (225 mg, 0.724 mmol), K2CO3 (415 mg, 3.0 mmol), and N,N-diisopropylethylamine (0.39 mL, 3.0 mmol) and the resultant suspension was heated at 80° C. for 16 h. The reaction was cooled to room temperature, diluted with satd. aq. NaHCO3 and extracted with ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate and concentrated. Purification by column chromatography (silica, 0-20% methanol/dichloromethane) afforded the desired product (180 mg, 52%) as an off-white solid. ESI MS m/z 474 [C24H29BrFN3O+H]+

1. temperatureThe reaction mixture was cooled to room temperature
2. additiondiluted with satd
3. extractionaq. sodium bicarbonate (50 mL) and 1 M aqueous sodium hydroxide (50 mL) and extracted with a mixture of CHCl3/isopropanol (3:1)
4. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
5. concentrationconcentrated
6. customto afford a white semisolid
7. temperatureThe reaction was cooled to room temperature
8. additiondiluted with satd
9. extractionaq. NaHCO3 and extracted with ethyl acetate
10. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
11. concentrationconcentrated
12. customPurification by column chromatography (silica, 0-20% methanol/dichloromethane)