Phenol → 4-Phenoxypyridine

Temperature

150 °C

Phenol (2.82 kg, 30.0 mol) was heated to 50° C. and 4-chloropyridine hydrochloride (1.5 kg, 10.0 mol) was added. The resulting solution was heated at 150° C. for 15 hours. The dark amber solution was cooled to 25° C. then poured into 3 M aqueous sodium hydroxide (16 L). The aqueous was extracted with dichloromethane (3×4 L). The combined organic was washed with 1 M sodium hydroxide (2×4 L), water (4 L), and brine (4 L) then dried over sodium sulfate and filtered. The solvent was removed under vacuum and the residual oil was dissolved in hexanes (6 L). The mixture was cooled to −60° C. with stirring and the resulting solid was collected by filtration and dried to give 1.1 kg of 4-phenoxypyridine (64% yield). mp 46-49° C. 1H NMR (300 MHz, CDCl3) δ 8.45 (dd, J=1.5, 8 Hz, 2H), 7.41 (dd, J=12, 12 Hz, 2H), 7.28 (dd, J=12, 1H), 7.06 (d, J=12 Hz, 2H), 6.84 (dd, J=1.5, 8 Hz, 2H).

1. temperatureThe dark amber solution was cooled to 25° C.
2. extractionThe aqueous was extracted with dichloromethane (3×4 L)
3. washThe combined organic was washed with 1 M sodium hydroxide (2×4 L), water (4 L), and brine (4 L)
4. dry with materialthen dried over sodium sulfate
5. filtrationfiltered
6. customThe solvent was removed under vacuum
7. dissolutionthe residual oil was dissolved in hexanes (6 L)
8. temperatureThe mixture was cooled to −60° C.
9. filtrationthe resulting solid was collected by filtration
10. customdried

ORD record

ord-e2ba74b36891404cbbe4ad4d126402ab

Source dataset

uspto-grants-2002_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06500948B1