反应详情

温度

100 °C

To the solution of 3-Fluoro-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzonitrile (306 mg, 1.24 mmol), 1-(3-Bromo-pyridin-4-yl)-ethanol (250 mg, 1.24 mmol) and PdCl2(dppf). CH2Cl2 adduct (81 mg, 0.10 mmol) in DMF (6 mL) was added 2M Na2CO3 solution (1.55 ml, 3.09 mmol) under Nitrogen atmosphere. The mixture was stirred and heated at 100° C. for 4 hrs. After letting cool to room temperature, solvent was removed in vacuo. The resulting residue was dissolved in DCM and saturated NH4Cl solution. After extraction with DCM and separation, the combined extracts were concentrated and purified by ISCO 12 g (10% MeOH/DCM=0-25%) to give 3-Fluoro-4-[4-(1-hydroxy-ethyl)-pyridin-3-yl]-benzonitrile (35 mg, 11%) as colorless solid; ESI-MS m/z: 243 [M+1]+, Retention time 1.19 min. 1H-NMR (MeOD, 400 MHz) δ 1.26 (d, J=6.8 Hz, 3H), 4.71 (q, J=6.8 Hz, 1H), 7.55 (t, J=8.0 Hz, 1H), 7.71 (dd, J=8.0, 1.6 Hz, 1H), 7.74 (d, J=9.6 Hz, 1H), 7.75 (d, J=5.2 Hz, 1H), 8.33 (s, 1H), 8.62 (d, J=5.2 Hz, 1H).

1. temperatureAfter letting cool to room temperature
2. customsolvent was removed in vacuo
3. dissolutionThe resulting residue was dissolved in DCM
4. extractionAfter extraction
5. customwith DCM and separation
6. concentrationthe combined extracts were concentrated
7. custompurified by ISCO 12 g (10% MeOH/DCM=0-25%)