Hydroxyamine hydrochloride → 2-Chloro-6-fluoro-4-hydroxybenzonitrile

Temperature

105 °C

A solution of 2-chloro-6-fluoro-4-hydroxybenzaldehyde (WO 2008141249, 90 mg, 0.344 mmol) in formic acid (1 mL) was treated with hydroxylamine hydrochloride (23.9 mg, 0.344 mmol) and sodium formate (23.4 mg, 0.344 mmol) and stirred under nitrogen for 3.5 hours at 105° C. The mixture was concentrated in vacuo and the residue treated with saturated aqueous sodium bicarbonate solution (10 mL). The aqueous solution was extracted with ethyl acetate (2×10 mL), dried over sodium sulphate and concentrated in vacuo. The residue was purified using silica gel column chromatography eluting with 30-50% EtOAc in heptanes to afford the title compound as a beige solid (33 mg, 56%).

1. concentrationThe mixture was concentrated in vacuo
2. additionthe residue treated with saturated aqueous sodium bicarbonate solution (10 mL)
3. extractionThe aqueous solution was extracted with ethyl acetate (2×10 mL)
4. dry with materialdried over sodium sulphate
5. concentrationconcentrated in vacuo
6. customThe residue was purified
7. washeluting with 30-50% EtOAc in heptanes

ORD record

ord-7c4afb027058457f87d1ff26f687dcdf

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09067922B2