Potassium Carbonate → 5-Bromo-2-chloro-4-(4-chlorophenyl)pyridine

Temperature

20 °C

To a degassed solution of 5-bromo-2-chloro-4-iodopyridine (Ref. Cottet, F. and Schlosser, M. Tetrahedron 60, 11896-11874 (2004)) (2.0 g, 6.3 mmol), 4-chlorophenylboronic acid (1.1 g, 6.9 mmol) and K2CO3 (1.7 g, 12.6 mmol) in 1,2-dimethoxyethane (24 mL) and H2O (8.0 mL) was added Pd(PPh3)4 (0.727 g, 0.63 mmol) under argon at 20° C. The reaction mixture was refluxed for 15 h under argon, then allowed to cool to 20° C. The reaction was quenched by addition of H2O (30 mL) and extracted with EtOAc (50 mL×3). The combined organic was washed with saturated aqueous NaHCO3 (50 mL) and saturated aqueous NaCl (50 mL), dried over MgSO4, filtered and concentrated in vacuo. The residue was crystallized in EtOH to afford 1.35 g of the title compound as a light beige solid as the first crop. The second crop of the title product (0.44 g) was also isolated by concentrating the mother liquid followed by recrystallization in EtOH. LC/MS (method B): retention time=2.03 min, [M+H]+=301.9.

1. temperatureThe reaction mixture was refluxed for 15 h under argon
2. customThe reaction was quenched by addition of H2O (30 mL)
3. extractionextracted with EtOAc (50 mL×3)
4. washThe combined organic was washed with saturated aqueous NaHCO3 (50 mL) and saturated aqueous NaCl (50 mL)
5. dry with materialdried over MgSO4
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customThe residue was crystallized in EtOH

ORD record

ord-91b5ab1cc8a34333b87b7b0ea770454a

Source dataset

uspto-grants-2010_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07858639B2