Ammonium Chloride → 4,5-Difluoro-1H-pyrrolo[2,3-b]pyridine

Temperature

-78 °C

4-fluoro-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridine (2.00 g, 6.84 mmol) in THF (20 mL) was added to s-BuLi (12.5 mL, 15.0 mmol, 1.4M in cyclohexane) at −78° C. for 30 minutes. N-Fluoro-N-(phenylsulfonyl)benzenesulfonamide (5.39 g, 17.1 mmol) in THF (15 mL) was added, and it was stirred at −78° C. for 20 minutes. A saturated ammonium chloride solution (20 mL) was added and extracted with hexanes (50 mL), washed with brine, and dried over sodium sulfate. After removal of the solvent, the residue was dissolved in THF (10 mL), and TBAF (6.84 mL, 6.84 mmol) in THF (6.84 mL, 6.84 mmol) was added. The reaction was stirred at room temperature for 10 minutes, and water (20 mL) and ethyl acetate (30 mL) were added. The organic layer was separated, washed with brine and dried over sodium sulfate. After removal of the solvent, the residue was purified by chromatography (ethyl acetate) to give 4,5-difluoro-1H-pyrrolo[2,3-b]pyridine (0.63 g, 60% yield) as a solid. LCMS (APCI+) m/z 155.1 (M+H)+.

1. extractionextracted with hexanes (50 mL)
2. washwashed with brine
3. dry with materialdried over sodium sulfate
4. customAfter removal of the solvent
5. dissolutionthe residue was dissolved in THF (10 mL)
6. stirringThe reaction was stirred at room temperature for 10 minutes
7. customThe organic layer was separated
8. washwashed with brine
9. dry with materialdried over sodium sulfate
10. customAfter removal of the solvent
11. customthe residue was purified by chromatography (ethyl acetate)

ORD record

ord-45c95415a0a04021a56cb552b61329fe

Source dataset

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08981085B2