反应详情

温度

120 °C

To a solution of 2,3,4,5-tetrahydro-2,8-dimethyl-1H-pyrido[4,3-b]indole (290 mg, 1.4 mmol) in DMF (6 mL) was added sodium hydride (38 mg, 1.6 mmol) and the solution was stirred at 120° C. for 1 h. The reaction mixture was cooled to 0° C. and 3-(2-methyloxiran-2-yl)pyridine (400 mg, 2.96 mmol) was added dropwise over a period of 5 min. The reaction mixture was stirred at 120° C. for 2 h, quenched with ice-water (15 mL) and extracted with EtOAc (60 mL). The organic layer was washed with water, brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by flash column chromatography (5-15% MeOH/EtOAc) to yield 1-(1,2,3,4-tetrahydro-2,8-dimethylpyrido[4,3-b]indol-5-yl)-2-(pyridin-3-yl)propan-2-ol. Separation by chiral HPLC provided enantiomers 5a and 5b. 1H NMR (CDCl3, freebase) δ (ppm): 8.79 (s, 1H), 8.42 (d, 1H), 7.56 (d, 1H), 7.04 (s, 1H), 6.9 (m, 2H), 6.8 (d, 1H), 4.17 (dd, 2H), 3.42 (s, 2H), 2.8 (t, 2H), 2.62 (t, 2H), 2.42 (s, 3H), 2.39 (s, 3H), 1.61 (s, 3H). Optical rotations: Compound 5a, (−)39.27 (c 0.43, Chloroform, 99.69% HPLC purity); Compound 5b, (+)58.97 (c 0.58, Chloroform, 99.49% HPLC purity).

1. temperatureThe reaction mixture was cooled to 0° C.
2. stirringThe reaction mixture was stirred at 120° C. for 2 h
3. customquenched with ice-water (15 mL)
4. extractionextracted with EtOAc (60 mL)
5. washThe organic layer was washed with water, brine
6. dry with materialdried over anhydrous sodium sulfate
7. concentrationconcentrated under reduced pressure
8. customThe residue was purified by flash column chromatography (5-15% MeOH/EtOAc)