反应详情

温度

99 °C

To a solution of 3-bromo-5-[[1-(tert-butoxycarbonyl)-2(S)-pyrrolidinyl]methoxy]pyridine (212 mg, 0.59 mmol) and 4-(2-phenoxyethyl)piperidine (134 mg, 0.65 mmol, 1.1 equiv.) in anhydrous toluene (5 mL) were added successively sodium tert-butoxide (85 mg, 0.89 mmol, 1.5 equiv.), tris(dibenzylideneacetone)dipalladium(0) (10.8 mg, 12 μmol, 0.02 equiv.), and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos; 20.6 mg, 37 μmol, 0.06 equiv.). The mixture was degassed and purged with Ar (3 cycles), then warmed to 98-100° C. for 4 h. After cooling to room temperature, the mixture was diluted with EtOAc, and the solution was washed with brine, dried over Na2SO4, and evaporated. The residue was purified by CC on SiO2 with CH2Cl2/EtOAc 4:1, then 1:1. The product (150 mg, 53%) was obtained as a pale yellow oil. 1H NMR (CDCl3, 400 MHz) δ 7.93-7.79 (m, 2H), 7.28 (t, 2H, J=8.0 Hz), 6.96-6.69 (m, 4H), 4.12 (m, 2H), 4.03 (t, 2H, J=6.0 Hz), 3.93-3.83 (m, 1H), 3.70 (m, 2H), 3.40 (m, 2H), 2.77 (m, 2H), 2.04-1.87 (m, 3H), 1.87-1.80 (m, 3H), 1.78-1.75 (m, 3H), 1.47 (s, 9H), 1.43-1.30 (m, 2H); 13C NMR (CDCl3, 100 MHz) δ 158.5, 155.1, 154.3, 148.0, 131.7, 130.9, 129.1, 127.8, 126.6, 120.2, 114.0, 108.7, 108.2, 79.4, 79.0, 68.4, 67.9, 64.8, 55.6, 48.7, 46.5, 46.2, 35.3, 32.2, 31.4, 28.1, 27.7, 23.4, 22.5.

1. customThe mixture was degassed
2. custompurged with Ar (3 cycles)
3. temperatureAfter cooling to room temperature
4. additionthe mixture was diluted with EtOAc
5. washthe solution was washed with brine
6. dry with materialdried over Na2SO4
7. customevaporated
8. customThe residue was purified by CC on SiO2 with CH2Cl2/EtOAc 4:1