Benzene → (6-Bromopyridin-3-yl)(phenyl)methanone

Temperature

5 °C

6-bromopyridine-3-carboxylic acid (50 g, 0.25 mol) in thionyl chloride (4a, 130 ml, 1.76 mol) was heated at reflux for 3 hours. The mixture was then concentrated under vacuum and the residue was co-evaporated with benzene to remove the thionyl chloride. The resulting acid chloride was dissolved in benzene (120 ml, 1.33 mol) and treated with AlCl3 (82.5 g, 0.6 mol) portion wise with stirring at 5° C. After heating at reflux for 6 hours, the reaction mixture was cooled to room temperature and poured into 20% HCl (500 ml), stirred for 1 h, and layers were separated. The aqueous layer was further extracted with ethyl acetate (3×100 mL). The combined organic layer was washed with brine, 50% KOH, and water (100 mL each), dried (Na2SO4), filtered and concentrated under reduced pressure to afford the product, 4-b, (50 g, 77%). 1H NMR (CDCl3, 300 MHz,): δ 8.72 (d, J=2.4 Hz, 1H), 8.04 (dd, J1=8.4 Hz, J2=2.7 Hz, 1H), 7.74 (m, 2H), 7.61 (m, 1H), 7.48 (m, 3H).

1. temperatureat reflux for 3 hours
2. concentrationThe mixture was then concentrated under vacuum
3. customto remove the thionyl chloride
4. temperatureAfter heating
5. temperatureat reflux for 6 hours
6. temperaturethe reaction mixture was cooled to room temperature
7. stirringstirred for 1 h
8. customlayers were separated
9. extractionThe aqueous layer was further extracted with ethyl acetate (3×100 mL)
10. washThe combined organic layer was washed with brine, 50% KOH, and water (100 mL each)
11. dry with materialdried (Na2SO4)
12. filtrationfiltered
13. concentrationconcentrated under reduced pressure

ORD record

ord-ffc0f72036f04fb293cae093bc31468e

Source dataset

uspto-grants-2015_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09079930B2