Ammonium Chloride → (5-Fluoro-2-nitrophenyl)-(3-fluoropyridin-2-yl)amine

Temperature

-78 °C

LiHMDS (1.0M in THF, 4.0 mL, 4.0 mmol) was added dropwise to a stirred solution of 2-amino-3-fluoropyridine (224 mg, 2.0 mmol) in anhydrous THF (5 mL) under a nitrogen atmosphere at −78° C. After 15 min stirring at −78° C., a solution of 2,4-difluoro-1-nitrobenzene (0.22 mL, 2.0 mmol) in THF (5 mL) was added and stirring at −78° C. was continued for 1 h. The mixture was slowly warmed to 0° C. and stirring continued for 1 h. The crude solution was poured into a saturated aqueous solution of NH4Cl (50 mL). The aqueous phase was extracted with EtOAc (×3) and the combined organic fractions were washed with water, followed by brine, dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, gradient 0-100% DCM in cyclohexane) to afford the title compound as an orange solid (93 mg, 19%). LCMS (Method C): RT 3.97 min [M+H]+ 252.10.

1. stirringstirring at −78° C.
2. waitwas continued for 1 h
3. temperatureThe mixture was slowly warmed to 0° C.
4. stirringstirring
5. waitcontinued for 1 h
6. extractionThe aqueous phase was extracted with EtOAc (×3)
7. washthe combined organic fractions were washed with water
8. dry with materialdried (Na2SO4)
9. concentrationconcentrated in vacuo
10. customThe resulting residue was purified by column chromatography (Si—PCC, gradient 0-100% DCM in cyclohexane)

ORD record

ord-e87f421dff174fcabe7a6d9269005e55

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08653089B2