Ethyl Acetate → 4-(5-(4-(2,5-Bis(4-nitrophenyl)pyrrolidin-1-yl)phenyl)pyridin-2-yl)morpholine

Participants

Reaction Steps

In a microwave tube (size L, 20 mL) purged with nitrogen and sealed with a rubber septum, dissolved the product of Example 86A (160 mg, 0.342 mmol) and 4-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]morpholine (153 mg, 0.512 mmol) in THF (6 mL), added a solution of potassium phosphate (176 mg, 0.803 mmol) in water (2 mL), and sparged the reaction solution with nitrogen for 5 min. Added 1,1′-bis(di-tert-butylphosphino)ferrocene palladium dichloride (12.02 mg, 0.018 mmol) and stirred at 25° C. for 15 min During this process, the reaction darkened quickly to a brown color. Diluted the reaction with EtOAc (50 mL), washed with brine (10 mL), dried the organic phase over anhydrous MgSO4, filtered, and concentrated by rotary evaporation. Dissolved the residue in CH2Cl2 and purified by flash chromatography (silica gel, Alltech Extract-Clean 10 g column, 20% EtOAc/CH2Cl2) to afford the title compound as a solid (176 mg, 93%) as a mixture of stereoisomers. 1H NMR (400 MHz, DMSO-D6) δ ppm 1.82-1.94 (m, 2 H), 2.53-2.62 (m, 2 H), 3.37-3.47 (m, 4 H), 3.64-3.74 (m, 4 H), 5.03 (t, J=5.37 Hz, 2 H), 6.40 (d, J=8.89 Hz, 2 H), 6.82 (d, J=9.00 Hz, 1 H), 7.34 (d, J=8.78 Hz, 2 H), 7.69 (dd, J=8.84, 2.55 Hz, 1 H), 7.83 (d, J=8.78 Hz, 4 H), 8.28 (d, J=8.78 Hz, 4 H), 8.29-8.31 (m, 1 H); MS (ESI+) m/z 552 (M+H)+.

Provenance & Evidence