反应详情

温度

0 °C

To a stirred solution of 3-(4,4-diphenylpiperidin-1-yl)propionitrile (5.00 g, 17.2 mmol, 1.00 equiv) in CH2Cl2 (40 mL) was added HCl in ether (1.0 M, 22.4 mL, 22 mmol, 1.3 equiv). After removal of the solvents, the residue and trimethyloxonium tetrafluoroborate (9.67 g, 65.4 mmol, 3.80 equiv) were stirred in refluxing anhydrous CH2Cl2 (80 mL) under argon for 44 hours. The mixture was cooled to 0° C., anhydrous MeOH (5 mL) was added, and stirring was continued for 1 hour at 0° C. The solvents were removed and the residue was dissolved in anhydrous MeOH (30 mL). Sodium borohydride (5.20 g, 138 mmol, 8.00 equiv) was added at 0° C., and stirring was continued at this temperature under argon for 2 hours. The solution was acidified to pH 1 by slow addition of 6 N aqueous HCl (40 mL) at 0° C. and stirred for 3 hours at room temperature. After removal of the solvents, water (30 mL) was added and the mixture was basified to pH 9 by addition of 6 N aqueous NaOH. The mixture was extracted with CH2Cl2 (3×100 mL), and the combined organic solutions were dried over MgSO4 and concentrated. The residue was purified by flash chromatography (SiO2, EtOAc-MeOH-isopropylamine 9:1:0 to 5:1:0.2) to give 2.18 g (41%) of yellow solid, which was characterized spectroscopically.

1. customAfter removal of the solvents
2. customThe solvents were removed
3. dissolutionthe residue was dissolved in anhydrous MeOH (30 mL)
4. stirringstirring
5. waitwas continued at this temperature under argon for 2 hours
6. stirringstirred for 3 hours at room temperature
7. customAfter removal of the solvents, water (30 mL)
8. additionwas added
9. additionthe mixture was basified to pH 9 by addition of 6 N aqueous NaOH
10. extractionThe mixture was extracted with CH2Cl2 (3×100 mL)
11. dry with materialthe combined organic solutions were dried over MgSO4
12. concentrationconcentrated
13. customThe residue was purified by flash chromatography (SiO2, EtOAc-MeOH-isopropylamine 9:1:0 to 5:1:0.2)