3-Bromopyridine → 3-(2-Fluorophenyl)pyridine

A mixture of 3-bromopyridine (3.37 mL, 5.53 g, 35 mmol), 2-fluorobenzeneboronic acid (6.12 g, 43.8 mmol) and potassium fluoride (6.71 g, 116 mmol) in THF (50 mL) was degassed with nitrogen for 10 min. Tris(dibenzylideneacetone)dipalladium(0) (0.64 g, 0.70 mmol) and tri(tert-butyl)phosphine (7 mL of a 0.2 M solution in dioxane, 1.4 mmol) were added. A solid precipitated, giving a thick slurry which was stirred under nitrogen for 15 min, then at 50° C. for 30 min. After cooling to room temperature, the mixture was partitioned between ethyl acetate and water. The organic phase was washed with saturated sodium chloride solution, then was dried over magnesium sulfate and pre-adsorbed on to silica gel. Purification by flash chromatography on silica gel eluting with isohexane (+0.5% methanol +0.5% triethylamine) on a gradient of 20% to 40% ethyl acetate afforded 3-(2-fluorophenyl)pyridine as a pale yellow oil, which crystallised upon standing. δH (360 MHz, DMSO) 7.33-7.40 (2H, m), 7.46-7.55 (2H, m), 7.61 (1H, ddd, J 8, 8 and 2), 7.96-8.01 (1H, m), 8.61 (1H, dd, J 5 and 2), 8.77 (1H, s).

1. customwas degassed with nitrogen for 10 min
2. customA solid precipitated
3. customgiving a thick slurry which
4. waitat 50° C. for 30 min
5. customthe mixture was partitioned between ethyl acetate and water
6. washThe organic phase was washed with saturated sodium chloride solution
7. dry with materialwas dried over magnesium sulfate and pre-adsorbed on to silica gel
8. customPurification by flash chromatography on silica gel eluting with isohexane (+0.5% methanol +0.5% triethylamine) on a gradient of 20% to 40% ethyl acetate

ORD 기록

ord-77d0f0ce534140a292257b3e0bdacce1

출처 데이터셋

uspto-grants-2005_11

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US06960598B2