反应详情

To a flask containing [1-cyclopropylmethyl-4-(4-iodo-phenyl)-piperidin-4-ylmethyl]-carbamic acid isobutyl ester (0.061 g, 0.13 mmol) was added Pd(PPh3)4 (0.015 g, 0.013 mmol, 10 mol %), 3-cyanophenylboronic acid (0.03 g, 0.2 mmol, 1.5 eq.) and Na2CO3 (0.212 g, 2 mmol). The mixture was suspended in toluene (3 mL), EtOH (1.5 mL) and H2O (1.0 mL) and heated to 80° C. for 18 h. The reaction mixture was cooled to room temperature and partitioned between EtOAc (10 mL) and saturated Na2CO3 (10 mL). The organic layer was washed with saturated Na2CO3 (3×10 mL) and saturated brine (2×10 mL), dried over anhydrous sodium sulfate, filtered and concentrated to give the crude product. This was purified by HPLC to give the title compound [4-(3′-cyano-biphenyl-4-yl)-1-cyclopropylmethyl-piperidin-4-ylmethyl]-carbamic acid isobutyl ester as a brown solid (0.014 g, 24%). MS (ESI): 446.3/447.3 (M+1).

1. custompartitioned between EtOAc (10 mL) and saturated Na2CO3 (10 mL)
2. washThe organic layer was washed with saturated Na2CO3 (3×10 mL) and saturated brine (2×10 mL)
3. dry with materialdried over anhydrous sodium sulfate
4. filtrationfiltered
5. concentrationconcentrated
6. customto give the crude product
7. customThis was purified by HPLC