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

A mixture of 2-chloro-4-(2,5-difluoro-4-nitrophenoxy)pyridine (3.57 g, 2.1 mmol), zinc dust (8.14 g, 125 mmol) and ammonium chloride (6.66 g, 125 mmol) in THF (160 mL) and MeOH (160 ml) was stirred at RT for 2 h. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure. The crude product was partitioned between EtOAc (50 ml) and a mixture of water and saturated NaHCO3 (aq) (1:1; 50 ml). The mixture was extracted with EtOAc (2×50 ml). The combined organic extracts were dried (Na2SO4) and evaporated to yield 4-(2-chloropyridin-4-yloxy)-2,5-difluoroaniline (3.18 g, 100% yield). 1H NMR (400 MHz, DMSO-d6): δ 8.26 (d, 1H), 7.24-7.19 (m, 1H), 7.00 (s, 1H), 6.94-6.92 (m, 1H), 6.74-6.69 (m, 1H), 5.54 (brs, 2H); MS (ESI) m/z: 257.0 (M+H+).

1. filtrationThe reaction mixture was filtered
2. concentrationthe filtrate was concentrated under reduced pressure
3. customThe crude product was partitioned between EtOAc (50 ml)
4. additiona mixture of water and saturated NaHCO3 (aq) (1:1; 50 ml)
5. extractionThe mixture was extracted with EtOAc (2×50 ml)
6. dry with materialThe combined organic extracts were dried (Na2SO4)
7. customevaporated

ORD record

ord-41bc0854d5064af6a1b60c8cab5011c6

Source dataset

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08486951B2