反应详情

温度

120 °C

tert-butyl 4-(((6-chloro-4-(trifluoromethyl)pyridine-2yl)methoxy)methyl)-4-phenylpiperidine-1-carboxylate (100 mg, 0.21 mmol), sodium tert-butoxide (22 mg, 0.23 mmol), N-methyl piperizine (18 mg, 0.18 mmol), (+/−) 2,2′-bis(diphenylphosphino)-1-1′-binaphthyl (93 mg, 0.15 mmol), and tris(dibenzylideneacetone)dipalladium (0) (7.0 mg, 0.007 mmol) were combined in dry toluene (2 mL) and dimethylformamide (0.5 mL) in a sealed tube. The mixture was then heated at 120° C. for 2 h. After cooling to room temperature, the reaction mixture was concentrated and treated with a trifluoroacetic acid/methylene chloride mixture (1:2, 2 mL) for 1 h. The solvent was removed in vacuo and the resulting crude mixture passed through a strong cation exchange column. After washing the column with several volumes of methanol, the product was eluted by washing the column with 2 M ammonia in methanol. Concentration and preparative HPLC afforded 31.0 mg (26%) of the desired compound as its TFA salt. 1H-NMR (CD3OD, 400 MHz) δ 7.27-7.46 (m, 5H), 6.99 (s, 1H), 6.74 (s, 1H), 4.40-4.53 (m, 2H), 4.40 (s, 2H), 3.50-3.55 (m, 4H), 3.10-3.50 (m, 6H), 2.83-2.96 (m, 5H), 2.51-2.55 (m, 2H), 2.15-2.22 (m, 2H), Mass spec.: 449.24 (MH)+.

1. temperatureAfter cooling to room temperature
2. concentrationthe reaction mixture was concentrated
3. additiontreated with a trifluoroacetic acid/methylene chloride mixture (1:2, 2 mL) for 1 h
4. customThe solvent was removed in vacuo
5. washAfter washing the column with several volumes of methanol
6. washthe product was eluted
7. washby washing the column with 2 M ammonia in methanol
8. concentrationConcentration and preparative HPLC