反应详情

温度

99 °C

To a solution of 3-bromo-5-[[1-(tert-butoxycarbonyl)-2(R)-pyrrolidinyl]methoxy]pyridine (264 mg, 0.74 mmol) and 4-[2-(4-fluorobenzyloxy)ethyl]piperidine (193 mg, 0.81 mmol, 1.1 equiv.) in anhydrous toluene (4 mL) were added successively sodium tert-butoxide (106 mg, 1.11 mmol, 1.5 equiv.), tris(dibenzylideneacetone)dipalladium(0) (13.5 mg, 15 μmol, 0.02 equiv.), and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos; 25.6 mg, 44 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. 3-[[1-(tert-Butoxycarbonyl)-2(S)-pyrrolidinyl]methoxy]-5-[4-[2-(4-fluorobenzyloxy)ethyl]-1-piperidinyl]pyridine (305 mg, 80%) was obtained as a pale yellow oil.

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