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 sulfate, filtered and pre-adsorbed onto silica. Purification by chromatography on silica eluting with isohexane (containing 0.5% methanol and 0.5% triethylamine) on a gradient of ethyl acetate (20-30%) gave 4-(2,6-difluorophenyl)pyridine as a white solid (3.2 g, 48%): δH (400 MHz, CDCl3) 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 sulfate
6. filtrationfiltered and pre-adsorbed onto silica
7. customPurification by chromatography on silica eluting with isohexane (containing 0.5% methanol and 0.5% triethylamine) on a gradient of ethyl acetate (20-30%)

ORD record

ord-8efa2faf665b4562aa441115eb3dbd21

Source dataset

uspto-grants-2005_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06960598B2