Pyridine → 4-bromo-3-nitro-1-[3-(trifluoromethyl)phenyl]-1H-pyrazole

Pyridine (99%, 0.512 mL, 6.27 mmol) and [3-(trifluoromethyl)phenyl]boronic acid (649 mg, 3.42 mmol) were added to a solution of 4-bromo-3-nitro-1H-pyrazole (596.6 mg, 3.108 mmol) in tetrahydrofuran (9 mL); copper(II) acetate (99%, 855 mg, 4.66 mmol) was then added, and the reaction was stirred for 42 hours. The reaction mixture was filtered through Celite and concentrated in vacuo, then partitioned between EtOAc (5 mL) and water (5 mL). The aqueous layer was extracted with EtOAc (3×5 mL), and the combined organic layers were washed with water (5 mL) and dried over sodium sulfate. After filtration and removal of solvent under reduced pressure, the residue was purified via silica gel chromatography (Gradient: 0% to 20% EtOAc in heptane) to provide C56. The regiochemistry of C56 was assigned based on NOE experiments. Yield: 779 mg, 2.32 mmol, 75%. GCMS m/z 335, 337 (M+). 1H NMR (400 MHz, CDCl3) δ 7.68-7.76 (m, 2H), 7.94-7.98 (m, 1H), 7.99-8.01 (m, 1H), 8.14 (s, 1H).

1. filtrationThe reaction mixture was filtered through Celite
2. concentrationconcentrated in vacuo
3. custompartitioned between EtOAc (5 mL) and water (5 mL)
4. extractionThe aqueous layer was extracted with EtOAc (3×5 mL)
5. washthe combined organic layers were washed with water (5 mL)
6. dry with materialdried over sodium sulfate
7. filtrationAfter filtration and removal of solvent under reduced pressure
8. customthe residue was purified via silica gel chromatography (Gradient: 0% to 20% EtOAc in heptane)
9. customto provide C56

ORD record

ord-0bb990fa222e49f695d7b95f97881ff3

Source dataset

uspto-grants-2015_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08933095B2