Sodium Hydroxide → HCID 10899450, compound

A suspension of 4-bromopyridine hydrochloride (6.81 g, 35 mmol) in tetrahydrofuran (100 ml) was treated with sodium hydroxide (8.75 ml of a 4 N solution in water) and this mixture was stirred at ambient temperature for 5 min. 2,6-Difluorobenzeneboronic acid (6.36 g, 40 mmol) and potassium fluoride (6.71 g, 116 mmol) were added and this mixture was degassed with nitrogen for 10 min before adding tris(dibenzylideneacetone)dipalladium(0) (640 mg, 0.7 mmol) followed by tri-tert-butylphosphine (7 ml of a 0.2 M solution in 1,4-dioxane, 1.4 mmol). This mixture was stirred at ambient temperature for 15 min then heated at 50° C. for 30 min. The reaction mixture was diluted with dichloromethane then extracted with ice-cold 1 N sodium hydroxide solution (×2). The organics were dried over anhydrous magnesium sulphate, filtered and pre-adsorbed onto silica. Purification by chromatography (silica gel, 20–30% EtOAc/isohexane containing 0.5% methanol and 0.5% triethylamine) gave 4-(2,6-difluorophenyl)pyridine as a white solid (3.2 g, 48%): 1H NMR (360 MHz, CDCl3) δ 6.99–7.06 (2H, m), 7.32–7.39 (1H, m), 7.40–7.42 (2H, m), 8.71 (2H, d, J 6).

1. customthis mixture was degassed with nitrogen for 10 min
2. stirringThis mixture was stirred at ambient temperature for 15 min
3. temperaturethen heated at 50° C. for 30 min
4. extractionthen extracted with ice-cold 1 N sodium hydroxide solution (×2)
5. dry with materialThe organics were dried over anhydrous magnesium sulphate
6. filtrationfiltered and pre-adsorbed onto silica
7. customPurification by chromatography (silica gel, 20–30% EtOAc/isohexane containing 0.5% methanol and 0.5% triethylamine)

ORD record

ord-319318fb3de2423098d8aa7c30edf509

Source dataset

uspto-grants-2006_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07005431B2