Potassium Carbonate → HCID 67383369, compound

Temperature

-78 °C

A solution of n-butyllithium (150 mL, 375 mmol) in 950 mL THF was cooled to −10° C. and treated with a solution of 2,2,6,6-tetramethylpiperidine (72.7 mL, 428 mmol) in 50 mL THF. After stirring for 15 min, the solution was cooled to −78° C. and 2-fluoro-5-iodopyridine (80 g, 357 mmol) was added as a solution in 400 mL THF dropwise via addition funnel over 60 minutes. After stirring for an additional 30 min, CO2 was bubbled through the red solution for 10 minutes. The cooling bath was removed, and CO2 was bubbled through the reaction mixture for an additional hour. The reaction mixture was concentrated in vacuo, triturated with hexanes and again concentrated in vacuo. The crude residue was taken up in 360 mL DMF and was treated with 4-bromo-3-fluorophenol (68.1 g, 357 mmol) followed by potassium carbonate (61.6 g, 446 mmol). The resulting mixture was heated to 120° C. for 18 h. The reaction mixture was cooled to rt and filtered through celite. The filtrate was diluted with EtOAc (500 mL) and was acidified to pH 3 with 6 N HCl. The organics were washed with water, brine, dried over MgSO4 and concentrated in vacuo. The crude residue was triturated with ether/hexanes, and the derived solid was dried under a stream of nitrogen to provide 2-(4-bromo-3-fluorophenoxy)-5-iodonicotinic acid (108.93 g, 249 mmol) as a brown solid.

1. stirringAfter stirring for an additional 30 min
2. customCO2 was bubbled through the red solution for 10 minutes
3. customThe cooling bath was removed
4. customCO2 was bubbled through the reaction mixture for an additional hour
5. concentrationThe reaction mixture was concentrated in vacuo
6. customtriturated with hexanes
7. concentrationagain concentrated in vacuo
8. temperatureThe resulting mixture was heated to 120° C. for 18 h
9. temperatureThe reaction mixture was cooled to rt
10. filtrationfiltered through celite
11. additionThe filtrate was diluted with EtOAc (500 mL)
12. washThe organics were washed with water, brine
13. dry with materialdried over MgSO4
14. concentrationconcentrated in vacuo
15. customThe crude residue was triturated with ether/hexanes
16. customthe derived solid was dried under a stream of nitrogen

ORD record

ord-e6ddc66f6205406399ed3dfd9fc08ac5

Source dataset

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08883782B2