2-Fluoropyridine → 2-((4-Bromobenzyl)oxy)pyridine

Temperature

22 °C

Under a nitrogen atmosphere, to a solution of 4-bromobenzyl alcohol (600 g, 3.21 mol) and 2-fluoropyridine (343 g, 3.53 mol) in tetrahydrofuran (1069 mL) was added a solution of potassium tert-butoxide (396 g, 3.53 mol) in tetrahydrofuran (3208 mL) (63 min, 9.2 to 20.5° C.) dropwise under a 7° C. cooling. After stirring at 22° C. for three hours, an aqueous solution of 5% sodium bicarbonate (prepared from sodium bicarbonate: 160 g and water: 3208 mL) was added thereto dropwise (20 min, 21.0 to 23.9° C.). Then, heptane (3220 mL) was added thereto and extracted, the organic layer was washed with water (800 mL). The organic layer was concentrated under a reduced pressure (to approximately 3200 mL), ethanol (1604 mL) was added thereto and concentrated under a reduced pressure (to approximately 3200 mL). Then, to the layer was added heptane (3200 mL), concentrated under a reduced pressure, heptane (3200 mL) was further added thereto and concentrated under a reduced pressure to obtain a solution of the title compound in heptane (2603 g, containing 789 g of the target product) as a brown oily product (yield: 93.2%).

1. temperaturecooling
2. customdropwise (20 min, 21.0 to 23.9° C.)
3. extractionextracted
4. washthe organic layer was washed with water (800 mL)
5. concentrationThe organic layer was concentrated under a reduced pressure (to approximately 3200 mL), ethanol (1604 mL)
6. additionwas added
7. concentrationconcentrated under a reduced pressure (to approximately 3200 mL)
8. additionThen, to the layer was added heptane (3200 mL)
9. concentrationconcentrated under a reduced pressure, heptane (3200 mL)
10. additionwas further added
11. concentrationconcentrated under a reduced pressure
12. customto obtain

ORD record

ord-dd104a8266814a2aa95253bfcd71cc9c

Source dataset

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08513287B2