Hydrochloric Acid → (6-Fluoropyridin-3-yl)boronic acid

Temperature

-42.5 °C

A 72 L reactor equipped with reflux condenser, and temperature probe. To the reactor 5-bromo-2-fluoropyridine (1.17 L, 0.568 mol), toluene (18.2 L), and triisopropyl borate (3.13 L, 0.68 mol, 1.2 equiv.) were charged and stirred. Tetrahydrofuran (4.4 L) was added to the reactor and the reaction mixture was cooled to between −35 to −50° C. While maintaining a temperature between −35 to −45° C., n-butyl lithium (2.5 M solution of hexanes, 5.44 L, 0.68 mol, 1.2 equiv.) was cautiously added to the reactor. After 5 h, the reaction was deemed complete and the reaction mixture was warmed to between −15 to −20° C. To the reaction was added 2M HCl (11.80 L) to the reactor while maintaining a temperature between −15° C. and 0° C. The reaction mixture was stirred at 18 to 23° C. for (16 h) and the phases were separated. The organics were then extracted with 6 M sodium hydroxide (6.0 L). The acidic anbasic aqueous phases were mixed in the reactor and 6 M HCl (2.5 L) was added until pH 7.5 was achieved. Sodium chloride (6.0 kg) was then added to the aqueous phase. The aqueous phase was then extracted with THF (3×20 L). The combined organics were dried with magnesium sulfate and concentrated to give 1300 g of a tan solid (81% crude yield).

1. customA 72 L reactor equipped
2. temperaturewith reflux condenser
3. temperatureWhile maintaining a temperature between −35 to −45° C.
4. temperaturethe reaction mixture was warmed to between −15 to −20° C
5. temperaturewhile maintaining a temperature between −15° C. and 0° C
6. stirringThe reaction mixture was stirred at 18 to 23° C. for (16 h)
7. customthe phases were separated
8. extractionThe organics were then extracted with 6 M sodium hydroxide (6.0 L)
9. additionThe acidic anbasic aqueous phases were mixed in the reactor and 6 M HCl (2.5 L)
10. additionwas added until pH 7.5
11. additionSodium chloride (6.0 kg) was then added to the aqueous phase
12. extractionThe aqueous phase was then extracted with THF (3×20 L)
13. dry with materialThe combined organics were dried with magnesium sulfate
14. concentrationconcentrated

ORD record

ord-b61dc1e920194d5bb767d14f6a5191b5

Source dataset

uspto-grants-2011_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07935697B2