反应详情

温度

80 °C

1-[4-(2-Chloro-3-methyl-pyridin-4-ylmethyl)-piperazin-1-yl]-ethanone (free base, 0.040 g, 0.15 mmol), NaOtBu (0.020 g, 0.21 mmol), BINAP (0.014 g, 0.020 mmol), and Pd2dba3 (0.0068 g, 0.0103 mmol) were stirred in 1 mL anhydrous toluene under N2. Benzophenone imine (0.030 mL, 0.18 mmol) was added and the reaction was heated to 80° C. After 3 h the reaction was cooled to RT, diluted with Et2O, filtered through celite, and concentrated in vacuo. To the residue was added 1:1 THF/1M HCl. The mixture was stirred for 2 h, then washed 2× w/EtOAc. The aqueous phase was adjusted to pH 10 with Na2CO3 (solid). The solution was extracted 3× with DCM/nBuOH (95:5), and the combined organic extracts were dried over Na2SO4, filtered, concentrated. The residue was purified by flash column chromatography (95:5-90:10 DCM/MeOH) to afford the pure titled compound. 1H NMR (CDCl3) δ7.89 (d, 1H, J=5.1 Hz), 6.65 (d, 1H, J=5.1 Hz), 4.45 (bs, 2H), 3.61 (t, 2H, J=4.9 Hz), 3.43 (m, 4H), 2.41 (t, 4H, J=5.2 Hz), 2.12 (s, 3H), 2.08 (s, 3H).

1. temperatureAfter 3 h the reaction was cooled to RT
2. filtrationfiltered through celite
3. concentrationconcentrated in vacuo
4. additionTo the residue was added 1:1 THF/1M HCl
5. washwashed 2× w/EtOAc
6. extractionThe solution was extracted 3× with DCM/nBuOH (95:5)
7. dry with materialthe combined organic extracts were dried over Na2SO4
8. filtrationfiltered
9. concentrationconcentrated
10. customThe residue was purified by flash column chromatography (95:5-90:10 DCM/MeOH)