反应详情

温度

120 °C

tert-butyl 4-(((6-chloro-4-(trifluoromethyl)pyridine-2yl)methoxy)methyl)-4-phenylpiperidine-1-carboxylate (100.0 mg, 0.21 mmol); 4-methoxyphenyl boronic acid (128.0 mg, 0.84 mmol), and tetrakis(triphenylphosphine)palladium(0) (48 mg, 0.04 mmol) were combined in dry tetrahydrofuran (3 mL) in a sealed tube. The mixture was flushed with nitrogen then 0.75 mL of a 1 N potassium hydroxide aqueous solution was introduced. The mixture was 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, 3 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 41.0 mg (34%) of the desired compound as its TFA salt. 1H-NMR (CD3OD, 400 MHz) δ 7.99 (d, 2H, J=8.0 Hz), 7.86 (s, 1H), 7.31-7.49 (m, 5H), 7.24 (s, 1H), 7.01 (d, 2H, J=8.0 Hz), 4.61 (s, 2H), 3.84 (s, 3H), 3.34 (s, 2H), 3.32-3.60 (m, 2H), 2.85-2.97 (m, 2H), 2.53-2.57 (m, 2H), 2.20-2.26 (m, 2H). Mass spec.: 457.18 (MH)+.

1. customThe mixture was flushed with nitrogen
2. addition0.75 mL of a 1 N potassium hydroxide aqueous solution was introduced
3. temperatureAfter cooling to room temperature
4. concentrationthe reaction mixture was concentrated
5. additiontreated with a trifluoroacetic acid/methylene chloride mixture (1:2, 3 mL) for 1 h
6. customThe solvent was removed in vacuo
7. washAfter washing the column with several volumes of methanol
8. washthe product was eluted
9. washby washing the column with 2 M ammonia in methanol
10. concentrationConcentration and preparative HPLC