Hydroxyamine hydrochloride → (NZ)-N-[1-(3,5-difluoro-2-pyridinyl)ethylidene]hydroxylamine

To a solution of 3,5-difluoropicolinonitrile (10.0 g, 71.4 mmol) in THF (200 ml) was added methylmagnesium bromide (61.2 ml, 85.7 mmol) in THF solution at 0° C. The reaction was stirred at room temperature for 1.5 hours. Saturated sodium bicarbonate solution (50 ml) was added, extracted with ether (100 ml), and dried over sodium sulfate. The solvent was removed. The residue (11.2 g, 71.28 mmol), hydroxylamine hydrochloride (9.907 g, 142.6 mmol) and sodium acetate (11.70 g, 142.6 mmol) in EtOH (100 ml) and water (50 ml) was heated at reflux for 3 hours. The solvent was removed and diluted with 50 ml of saturated sodium bicarbonate and extracted with EtOAc (2×200 ml). After dried over sodium sulfate, the solvent was removed and the title compound was used directly in next step without purification.

1. extractionextracted with ether (100 ml)
2. dry with materialdried over sodium sulfate
3. customThe solvent was removed
4. temperatureat reflux for 3 hours
5. customThe solvent was removed
6. additiondiluted with 50 ml of saturated sodium bicarbonate
7. extractionextracted with EtOAc (2×200 ml)
8. dry with materialAfter dried over sodium sulfate
9. customthe solvent was removed
10. customthe title compound was used directly in next step without purification

ORD record

ord-0e0943ac21074b589f5b951b6e2fdf17

Source dataset

uspto-grants-2012_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08324252B2