Tetrahydrofuran → Benzenamine, 4-[(2-chloro-4-pyridinyl)oxy]-2,5-difluoro-

2-Chloro-4-(2,5-difluoro-4-nitrophenoxy)pyridine (13.06 g, 45.6 mmol) was dissolved in methanol (228 mL) and THF (228 mL) and cooled in an ice bath. Ammonium chloride (24.37 g, 456 mmol) was added, followed by zinc dust (29.8 g, 456 mmol), and the mixture was stirred in an ice bath for 30 minutes. After 30 minutes the ice bath was removed and the reaction mixture was allowed to warm to room temperature. After an additional hour of stirring the mixture was filtered through Celite®, which was washed well with methanol. The filtrate was concentrated under reduced pressure and the residue was partitioned between ethyl acetate (200 mL) and water (100 mL). The organic layer was washed with additional water (50 mL) and brine (100 mL), dried over magnesium sulfate, and concentrated to give 4-(2-chloropyridin-4-yloxy)-2,5-difluorobenzenamine (11.60 g, 99% yield) as a light brown solid. MS (ESI) m/z: 257.0 (M+H+).

1. customAfter 30 minutes the ice bath was removed
2. stirringAfter an additional hour of stirring the mixture
3. filtrationwas filtered through Celite®, which
4. washwas washed well with methanol
5. concentrationThe filtrate was concentrated under reduced pressure
6. customthe residue was partitioned between ethyl acetate (200 mL) and water (100 mL)
7. washThe organic layer was washed with additional water (50 mL) and brine (100 mL)
8. dry with materialdried over magnesium sulfate
9. concentrationconcentrated

ORD record

ord-393cc965cfad40a58b43653cb77247b6

Source dataset

uspto-grants-2014_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08637672B2